Skip to main content
Erschienen in:

Open Access 16.06.2016 | ORIGINAL ARTICLE

Vasodilator Therapy: Nitrates and Nicorandil

verfasst von: Jason M. Tarkin, Juan Carlos Kaski

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3′,-5′-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K+ ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.
Literatur
1.
Zurück zum Zitat Murrell W. Nitro-glycerine as a remedy for angina pectoris. Lancet Elsevier. 1879;113:225–7.CrossRef Murrell W. Nitro-glycerine as a remedy for angina pectoris. Lancet Elsevier. 1879;113:225–7.CrossRef
2.
Zurück zum Zitat Task Force Members, Montalescot, G, Sechtem, U, Achenbach, S, Andreotti, F, Arden, C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013. pp. 2949–3003. Task Force Members, Montalescot, G, Sechtem, U, Achenbach, S, Andreotti, F, Arden, C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013. pp. 2949–3003.
3.
Zurück zum Zitat Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and Management of Patients with Stable Ischemic Heart Disease. J Am Coll Cardiol Elsevier Inc. 2012;60:e44–e164.CrossRef Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and Management of Patients with Stable Ischemic Heart Disease. J Am Coll Cardiol Elsevier Inc. 2012;60:e44–e164.CrossRef
4.
Zurück zum Zitat Parker JD, Parker JO. Nitrate therapy for stable angina pectoris. N Engl J Med. 1998;338:520–31.PubMedCrossRef Parker JD, Parker JO. Nitrate therapy for stable angina pectoris. N Engl J Med. 1998;338:520–31.PubMedCrossRef
5.
Zurück zum Zitat Murad F. Discovery of some of the biological effects of nitric oxide and its role in cell signaling. Biosci Rep. 2005;24:452–74.CrossRef Murad F. Discovery of some of the biological effects of nitric oxide and its role in cell signaling. Biosci Rep. 2005;24:452–74.CrossRef
6.
Zurück zum Zitat Ignarro LJ. Nitric oxide: a unique endogenous signaling molecule in vascular biology. Biosci Rep Kluwer Acad Publishers-Plenum Publishers. 1999;19:51–71. Ignarro LJ. Nitric oxide: a unique endogenous signaling molecule in vascular biology. Biosci Rep Kluwer Acad Publishers-Plenum Publishers. 1999;19:51–71.
7.
Zurück zum Zitat Furchgott RF. Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide. Biosci Rep Kluwer Acad Publishers-Plenum Publishers. 1999;19:235–51. Furchgott RF. Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide. Biosci Rep Kluwer Acad Publishers-Plenum Publishers. 1999;19:235–51.
8.
Zurück zum Zitat Thatcher GRJ, Nicolescu AC, Bennett BM, Toader V. Nitrates and no release: contemporary aspects in biological and medicinal chemistry. Free Radic Biol Med. 2004;37:1122–43.PubMedCrossRef Thatcher GRJ, Nicolescu AC, Bennett BM, Toader V. Nitrates and no release: contemporary aspects in biological and medicinal chemistry. Free Radic Biol Med. 2004;37:1122–43.PubMedCrossRef
9.
Zurück zum Zitat Gori T, Parker JD. Nitrate-induced toxicity and preconditioning. J Am Coll Cardiol. 2008;52:251–4.PubMedCrossRef Gori T, Parker JD. Nitrate-induced toxicity and preconditioning. J Am Coll Cardiol. 2008;52:251–4.PubMedCrossRef
10.
Zurück zum Zitat Kukovetz WR, Holzmann S, Braida C, Pöch G. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolarization. J Cardiovasc Pharmacol. 1991;17:627–33.PubMedCrossRef Kukovetz WR, Holzmann S, Braida C, Pöch G. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolarization. J Cardiovasc Pharmacol. 1991;17:627–33.PubMedCrossRef
11.
Zurück zum Zitat Horinaka DS. Use of nicorandil in cardiovascular disease and its optimization. Drugs Springer Int Publ. 2011;71:1105–19. Horinaka DS. Use of nicorandil in cardiovascular disease and its optimization. Drugs Springer Int Publ. 2011;71:1105–19.
12.
Zurück zum Zitat Tarkin JM, Kaski JC. Pharmacological treatment of chronic stable angina pectoris. Clin Med Royal Coll Physicians. 2013;13:63–70. Tarkin JM, Kaski JC. Pharmacological treatment of chronic stable angina pectoris. Clin Med Royal Coll Physicians. 2013;13:63–70.
13.
Zurück zum Zitat Belsey J, Savelieva I, Mugelli A, Camm AJ. Relative efficacy of antianginal drugs used as add-on therapy in patients with stable angina: a systematic review and meta-analysis. Eur J Prev Cardiol. 2015;22:837–48.PubMedCrossRef Belsey J, Savelieva I, Mugelli A, Camm AJ. Relative efficacy of antianginal drugs used as add-on therapy in patients with stable angina: a systematic review and meta-analysis. Eur J Prev Cardiol. 2015;22:837–48.PubMedCrossRef
14.
Zurück zum Zitat Lanza GA, Parrinello R, Figliozzi S. Management of microvascular angina pectoris. Am J Cardiovasc drugs. Springer International Publishing. 2014;14:31–40. Lanza GA, Parrinello R, Figliozzi S. Management of microvascular angina pectoris. Am J Cardiovasc drugs. Springer International Publishing. 2014;14:31–40.
15.
Zurück zum Zitat Maseri A, Chierchia S, Kaski JC. Mixed angina pectoris. AJC. 1985;56:30E–3E.CrossRef Maseri A, Chierchia S, Kaski JC. Mixed angina pectoris. AJC. 1985;56:30E–3E.CrossRef
16.
Zurück zum Zitat Kaski JC. Management of vasospastic angina–role of nicorandil. Cardiovasc Drugs Ther. 1995;9(Suppl 2):221–7.PubMedCrossRef Kaski JC. Management of vasospastic angina–role of nicorandil. Cardiovasc Drugs Ther. 1995;9(Suppl 2):221–7.PubMedCrossRef
17.
Zurück zum Zitat Fung HL, Chung SJ, Bauer JA, Chong S, Kowaluk EA. Biochemical mechanism of organic nitrate action. AJC. 1992;70:4B–10B.CrossRef Fung HL, Chung SJ, Bauer JA, Chong S, Kowaluk EA. Biochemical mechanism of organic nitrate action. AJC. 1992;70:4B–10B.CrossRef
18.
Zurück zum Zitat Heidenreich PA, McDonald KM, Hastie T, Fadel B, Hagan V, Lee BK, et al. Meta-analysis of trials comparing β-blockers, calcium antagonists, and nitrates for stable angina. JAMA Am Med Assoc. 1999;281:1927–36.CrossRef Heidenreich PA, McDonald KM, Hastie T, Fadel B, Hagan V, Lee BK, et al. Meta-analysis of trials comparing β-blockers, calcium antagonists, and nitrates for stable angina. JAMA Am Med Assoc. 1999;281:1927–36.CrossRef
19.
Zurück zum Zitat Münzel T, Meinertz T, Tebbe U, Schneider HT, Stalleicken D, Wargenau M, et al. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial. Eur Heart J. 2014;35:895–903.PubMedCrossRef Münzel T, Meinertz T, Tebbe U, Schneider HT, Stalleicken D, Wargenau M, et al. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial. Eur Heart J. 2014;35:895–903.PubMedCrossRef
20.
Zurück zum Zitat Munzel T. Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3″,5-”cyclic monophosphate-dependent protein kinase. Circulation. 2003;108:2172–83.PubMedCrossRef Munzel T. Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3″,5-”cyclic monophosphate-dependent protein kinase. Circulation. 2003;108:2172–83.PubMedCrossRef
21.
Zurück zum Zitat Palmer R, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–6.PubMedCrossRef Palmer R, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–6.PubMedCrossRef
22.
Zurück zum Zitat Suk-Jae C, Ho-Leung F. Relationship between nitroglycerin-induced vascular relaxation and nitric oxide production: probes with inhibitors and tolerance development. Biochem Pharmacol. 1993;45:157–63.CrossRef Suk-Jae C, Ho-Leung F. Relationship between nitroglycerin-induced vascular relaxation and nitric oxide production: probes with inhibitors and tolerance development. Biochem Pharmacol. 1993;45:157–63.CrossRef
23.
Zurück zum Zitat Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–51.PubMedCrossRef Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–51.PubMedCrossRef
24.
Zurück zum Zitat Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ, Ganz P, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 1991;325:1551–6.PubMedCrossRef Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ, Ganz P, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 1991;325:1551–6.PubMedCrossRef
25.
Zurück zum Zitat Thadani U. Oral nitrates: more than symptomatic therapy in coronary artery disease? Cardiovasc Drugs Ther. 1997;11(Suppl 1):213–8.PubMedCrossRef Thadani U. Oral nitrates: more than symptomatic therapy in coronary artery disease? Cardiovasc Drugs Ther. 1997;11(Suppl 1):213–8.PubMedCrossRef
26.
Zurück zum Zitat Mayer B, Beretta M. The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles. Br J Pharmacol. 2009;155:170–84.CrossRef Mayer B, Beretta M. The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles. Br J Pharmacol. 2009;155:170–84.CrossRef
27.
Zurück zum Zitat Kleschyov AL. Does nitric oxide mediate the vasodilator activity of nitroglycerin? Circ Res. 2003;93:104e–112.CrossRef Kleschyov AL. Does nitric oxide mediate the vasodilator activity of nitroglycerin? Circ Res. 2003;93:104e–112.CrossRef
28.
Zurück zum Zitat Nunez C. Discrepancies between nitroglycerin and NO-releasing drugs on mitochondrial oxygen consumption, vasoactivity, and the release of NO. Circ Res. 2005;97:1063–9.PubMedCrossRef Nunez C. Discrepancies between nitroglycerin and NO-releasing drugs on mitochondrial oxygen consumption, vasoactivity, and the release of NO. Circ Res. 2005;97:1063–9.PubMedCrossRef
29.
Zurück zum Zitat Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc. Natl. Acad. Sci. U.S.A. Natl Acad Sci. 2002;99:8306–11.CrossRef Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc. Natl. Acad. Sci. U.S.A. Natl Acad Sci. 2002;99:8306–11.CrossRef
30.
Zurück zum Zitat Chen Z, Stamler JS. Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med. 2006;16:259–65.PubMedCrossRef Chen Z, Stamler JS. Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med. 2006;16:259–65.PubMedCrossRef
31.
Zurück zum Zitat Li Y. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. J Clin Investig. 2006;116:506–11.PubMedPubMedCentralCrossRef Li Y. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. J Clin Investig. 2006;116:506–11.PubMedPubMedCentralCrossRef
32.
Zurück zum Zitat Munzel T, Daiber A, Gori T. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. 2011;123:2132–44.PubMedCrossRef Munzel T, Daiber A, Gori T. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. 2011;123:2132–44.PubMedCrossRef
33.
Zurück zum Zitat Daiber A, Oelze M, Coldewey M, Bachschmid M, Wenzel P, Sydow K, et al. Oxidative stress and mitochondrial aldehyde dehydrogenase activity: a comparison of pentaerythritol tetranitrate with other organic nitrates. Mol Pharmacol. 2004;66:1372–82.PubMedCrossRef Daiber A, Oelze M, Coldewey M, Bachschmid M, Wenzel P, Sydow K, et al. Oxidative stress and mitochondrial aldehyde dehydrogenase activity: a comparison of pentaerythritol tetranitrate with other organic nitrates. Mol Pharmacol. 2004;66:1372–82.PubMedCrossRef
34.
Zurück zum Zitat Daiber A, Wenzel P, Oelze M, Münzel T. New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance. Clin Res Cardiol. 2007;97:12–20.PubMedCrossRef Daiber A, Wenzel P, Oelze M, Münzel T. New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance. Clin Res Cardiol. 2007;97:12–20.PubMedCrossRef
35.
Zurück zum Zitat Torfgård KE, Ahlner J. Mechanisms of action of nitrates. Cardiovasc Drugs Ther. 1994;8:701–17.PubMedCrossRef Torfgård KE, Ahlner J. Mechanisms of action of nitrates. Cardiovasc Drugs Ther. 1994;8:701–17.PubMedCrossRef
36.
Zurück zum Zitat Morgado M, Cairrão E, Santos-Silva AJ, Verde I. Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci. 2012;69:247–66.PubMedCrossRef Morgado M, Cairrão E, Santos-Silva AJ, Verde I. Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci. 2012;69:247–66.PubMedCrossRef
37.
Zurück zum Zitat Abrams J. Beneficial actions of nitrates in cardiovascular disease. Am J Cardiol. 1996. Abrams J. Beneficial actions of nitrates in cardiovascular disease. Am J Cardiol. 1996.
38.
Zurück zum Zitat Feldman RL, Pepine CJ, Conti CR. Magnitude of dilatation of large and small coronary arteries of nitroglycerin. Circulation. 1981;64:324–33.PubMedCrossRef Feldman RL, Pepine CJ, Conti CR. Magnitude of dilatation of large and small coronary arteries of nitroglycerin. Circulation. 1981;64:324–33.PubMedCrossRef
39.
Zurück zum Zitat Münzel T, Gori T. Nitrate therapy and nitrate tolerance in patients with coronary artery disease. Curr Opin Pharmacol Elsevier Ltd. 2013;13:251–9.CrossRef Münzel T, Gori T. Nitrate therapy and nitrate tolerance in patients with coronary artery disease. Curr Opin Pharmacol Elsevier Ltd. 2013;13:251–9.CrossRef
40.
Zurück zum Zitat Tousoulis D, Davies GJ, Toutouzas PC. Vasomotion of coronary arteries: from nitrates to nitric oxide. Cardiovasc Drugs Ther. Kluwer Academic Publishers. 1999;13:295–300.CrossRef Tousoulis D, Davies GJ, Toutouzas PC. Vasomotion of coronary arteries: from nitrates to nitric oxide. Cardiovasc Drugs Ther. Kluwer Academic Publishers. 1999;13:295–300.CrossRef
41.
Zurück zum Zitat Abrams J. Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol. 1992;70:B30–42.CrossRef Abrams J. Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol. 1992;70:B30–42.CrossRef
42.
Zurück zum Zitat Brown BG, Lee AB, Bolson EL, Dodge HT. Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circn Lippincott Williams & Wilkins. 1984;70:18–24. Brown BG, Lee AB, Bolson EL, Dodge HT. Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circn Lippincott Williams & Wilkins. 1984;70:18–24.
43.
Zurück zum Zitat Fujita M, Yamanishi K, Inoko M. Preferential dilation of recipient coronary arteries of the collateral circulation by intracoronary administration of nitroglycerin. J Am Coll Cardiol 1994. Fujita M, Yamanishi K, Inoko M. Preferential dilation of recipient coronary arteries of the collateral circulation by intracoronary administration of nitroglycerin. J Am Coll Cardiol 1994.
44.
Zurück zum Zitat Brown BG, Bolson E, Petersen RB, Pierce CD, Dodge HT. The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response. Circulation. 1981;64:1089–97.PubMedCrossRef Brown BG, Bolson E, Petersen RB, Pierce CD, Dodge HT. The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response. Circulation. 1981;64:1089–97.PubMedCrossRef
45.
Zurück zum Zitat Sidhu M, Boden WE, Padala SK, Cabral K, Buschmann I. Role of short-acting nitroglycerin in the management of ischemic heart disease. DDDT. 2015;4793–13. Sidhu M, Boden WE, Padala SK, Cabral K, Buschmann I. Role of short-acting nitroglycerin in the management of ischemic heart disease. DDDT. 2015;4793–13.
46.
Zurück zum Zitat Fallen EL, Nahmias C, Scheffel A, Coates G, Beanlands R, Garnett ES. Redistribution of myocardial blood flow with topical nitroglycerin in patients with coronary artery disease. Circ Lippincott Williams & Wilkins. 1995;91:1381–8. Fallen EL, Nahmias C, Scheffel A, Coates G, Beanlands R, Garnett ES. Redistribution of myocardial blood flow with topical nitroglycerin in patients with coronary artery disease. Circ Lippincott Williams & Wilkins. 1995;91:1381–8.
47.
Zurück zum Zitat Horwitz LD, Gorlin R, Taylor WJ, Kemp HG. Effects of nitroglycerin on regional myocardial blood flow in coronary artery disease. J Clin Invest Am Soc Clin Invest. 1971;50:1578–84.CrossRef Horwitz LD, Gorlin R, Taylor WJ, Kemp HG. Effects of nitroglycerin on regional myocardial blood flow in coronary artery disease. J Clin Invest Am Soc Clin Invest. 1971;50:1578–84.CrossRef
48.
Zurück zum Zitat Imhof PR, Sieber A, Hodler J, Müller P, Ott B, Fankhauser P, et al. Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers. Eur J Clin Pharmacol. 1982;23:99–106.PubMedCrossRef Imhof PR, Sieber A, Hodler J, Müller P, Ott B, Fankhauser P, et al. Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers. Eur J Clin Pharmacol. 1982;23:99–106.PubMedCrossRef
49.
Zurück zum Zitat Hampton JR, Harrison MJ, Honour AJ, Mitchell JR. Platelet behaviour and drugs used in cardiovascular disease. Cardiovasc Res. 1967;1:101–7.PubMedCrossRef Hampton JR, Harrison MJ, Honour AJ, Mitchell JR. Platelet behaviour and drugs used in cardiovascular disease. Cardiovasc Res. 1967;1:101–7.PubMedCrossRef
50.
Zurück zum Zitat Zhou R-H, Frishman WH. The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease? Cardiol Rev. 2010;18:198–203.PubMedCrossRef Zhou R-H, Frishman WH. The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease? Cardiol Rev. 2010;18:198–203.PubMedCrossRef
51.
Zurück zum Zitat Salvemini D, Currie MG, Mollace V. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators. J Clin Investig. 1996;97:2562–8.PubMedPubMedCentralCrossRef Salvemini D, Currie MG, Mollace V. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators. J Clin Investig. 1996;97:2562–8.PubMedPubMedCentralCrossRef
52.
Zurück zum Zitat Stamler JS, Loscalzo J. The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders. J Am Coll Cardiol. 1991;18:1529–36.PubMedCrossRef Stamler JS, Loscalzo J. The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders. J Am Coll Cardiol. 1991;18:1529–36.PubMedCrossRef
53.
Zurück zum Zitat Diodati J, Theroux P, Latour JG, Lacoste L, Lam JY, Waters D. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction. AJC. 1990;66:683–8.CrossRef Diodati J, Theroux P, Latour JG, Lacoste L, Lam JY, Waters D. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction. AJC. 1990;66:683–8.CrossRef
54.
Zurück zum Zitat GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet. 1994;343:1115–22. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet. 1994;343:1115–22.
55.
Zurück zum Zitat ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet. 1995;345:669–85. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet. 1995;345:669–85.
56.
Zurück zum Zitat Jneid H, Chandra M, Alshaher M, Hornung CA, Tang X-L, Leesar M, et al. Delayed preconditioning-mimetic actions of nitroglycerin in patients undergoing exercise tolerance tests. Circulation. 2005;111:2565–71.PubMedCrossRef Jneid H, Chandra M, Alshaher M, Hornung CA, Tang X-L, Leesar M, et al. Delayed preconditioning-mimetic actions of nitroglycerin in patients undergoing exercise tolerance tests. Circulation. 2005;111:2565–71.PubMedCrossRef
57.
Zurück zum Zitat Hill M, Takano H, Tang XL, Kodani E, Shirk G, Bolli R. Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance. Circulation. 2001;104:694–9.PubMedCrossRef Hill M, Takano H, Tang XL, Kodani E, Shirk G, Bolli R. Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance. Circulation. 2001;104:694–9.PubMedCrossRef
58.
Zurück zum Zitat Gori T, Di Stolfo G, Sicuro S, Dragoni S, Lisi M, Forconi S, et al. Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight. Br J Clin Pharmacol. 2007;64:145–50.PubMedPubMedCentralCrossRef Gori T, Di Stolfo G, Sicuro S, Dragoni S, Lisi M, Forconi S, et al. Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight. Br J Clin Pharmacol. 2007;64:145–50.PubMedPubMedCentralCrossRef
59.
Zurück zum Zitat Banerjee S, Tang XL, Qiu Y, Takano H, Manchikalapudi S, Dawn B, et al. Nitroglycerin induces late preconditioning against myocardial stunning via a PKC-dependent pathway. Am J Phys. 1999;277:H2488–94. Banerjee S, Tang XL, Qiu Y, Takano H, Manchikalapudi S, Dawn B, et al. Nitroglycerin induces late preconditioning against myocardial stunning via a PKC-dependent pathway. Am J Phys. 1999;277:H2488–94.
60.
Zurück zum Zitat Murphy E. Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection. Circ Res. 2004;94:7–16.PubMedCrossRef Murphy E. Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection. Circ Res. 2004;94:7–16.PubMedCrossRef
61.
Zurück zum Zitat Ambrosio G, Del Pinto M, Tritto I, Agnelli G, Bentivoglio M, Zuchi C, et al. Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52 693 patients in the global registry of acute coronary events. Eur Heart J. 2010;31:430–8.PubMedCrossRef Ambrosio G, Del Pinto M, Tritto I, Agnelli G, Bentivoglio M, Zuchi C, et al. Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52 693 patients in the global registry of acute coronary events. Eur Heart J. 2010;31:430–8.PubMedCrossRef
62.
Zurück zum Zitat Timóteo AT, Mamede A, Ferreira ML, Serra J. A terapêutica crónica com nitratos está associada a uma diferente apresentação clínica de síndroma coronária aguda? 2007. Timóteo AT, Mamede A, Ferreira ML, Serra J. A terapêutica crónica com nitratos está associada a uma diferente apresentação clínica de síndroma coronária aguda? 2007.
63.
Zurück zum Zitat Giuseppe C, Paul J, Hans-Ulrich I. Use of nitrates in ischemic heart disease. Expert Opin Pharmacother. 2015;16:1567–72.PubMedCrossRef Giuseppe C, Paul J, Hans-Ulrich I. Use of nitrates in ischemic heart disease. Expert Opin Pharmacother. 2015;16:1567–72.PubMedCrossRef
64.
Zurück zum Zitat Zimrin D, Reichek N, Bogin KT, Aurigemma G, Douglas P, Berko B, et al. Antianginal effects of intravenous nitroglycerin over 24 hours. Circulation. 1988;77:1376–84.PubMedCrossRef Zimrin D, Reichek N, Bogin KT, Aurigemma G, Douglas P, Berko B, et al. Antianginal effects of intravenous nitroglycerin over 24 hours. Circulation. 1988;77:1376–84.PubMedCrossRef
65.
Zurück zum Zitat Thadani U. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance. Am J Cardiovasc Drugs. 2014;14:287–301.PubMedCrossRef Thadani U. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance. Am J Cardiovasc Drugs. 2014;14:287–301.PubMedCrossRef
66.
67.
Zurück zum Zitat DiFabio J, Ji Y, Vasiliou V, Thatcher GRJ, Bennett BM. Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance. Mol Pharmacol Am Soc Pharmacol and Exp Ther. 2003;64:1109–16. DiFabio J, Ji Y, Vasiliou V, Thatcher GRJ, Bennett BM. Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance. Mol Pharmacol Am Soc Pharmacol and Exp Ther. 2003;64:1109–16.
68.
Zurück zum Zitat Gori T, Daiber A. Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate. Am J Cardiovasc Drugs Lippincott Williams & Wilkins. 2009;9:7–15.CrossRef Gori T, Daiber A. Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate. Am J Cardiovasc Drugs Lippincott Williams & Wilkins. 2009;9:7–15.CrossRef
69.
Zurück zum Zitat Ishikawa K, Kanamasa K, Ogawa I, Takenaka T, Naito T, Kamata N, et al. Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group Jpn Circ J. 1996;60:779–88.PubMedCrossRef Ishikawa K, Kanamasa K, Ogawa I, Takenaka T, Naito T, Kamata N, et al. Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group Jpn Circ J. 1996;60:779–88.PubMedCrossRef
70.
Zurück zum Zitat Nakamura Y, Moss AJ, Brown MW, Kinoshita M, Kawai C. Long-term nitrate use may be deleterious in ischemic heart disease: a study using the databases from two large-scale postinfarction studies. Multicenter myocardial ischemia research group. Am Heart J. 1999;138:577–85.PubMedCrossRef Nakamura Y, Moss AJ, Brown MW, Kinoshita M, Kawai C. Long-term nitrate use may be deleterious in ischemic heart disease: a study using the databases from two large-scale postinfarction studies. Multicenter myocardial ischemia research group. Am Heart J. 1999;138:577–85.PubMedCrossRef
71.
Zurück zum Zitat Thomas GR, DiFabio JM, Gori T, Parker JD. Once daily therapy with isosorbide-5-mononitrate causes endothelial dysfunction in humans: evidence of a free-radical-mediated mechanism. J Am Coll Cardiol. 2007;49:1289–95.PubMedCrossRef Thomas GR, DiFabio JM, Gori T, Parker JD. Once daily therapy with isosorbide-5-mononitrate causes endothelial dysfunction in humans: evidence of a free-radical-mediated mechanism. J Am Coll Cardiol. 2007;49:1289–95.PubMedCrossRef
72.
Zurück zum Zitat Caramori PR, Adelman AG, Azevedo ER, Newton GE, Parker AB, Parker JD. Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine. J Am Coll Cardiol. 1998;32:1969–74.PubMedCrossRef Caramori PR, Adelman AG, Azevedo ER, Newton GE, Parker AB, Parker JD. Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine. J Am Coll Cardiol. 1998;32:1969–74.PubMedCrossRef
73.
Zurück zum Zitat Munzel T, Mollnau H, Hartmann M, Geiger C, Oelze M, Warnholtz A, et al. Effects of a nitrate-free interval on tolerance, vasoconstrictor sensitivity and vascular superoxide production. J Am Coll Cardiol. 2000;36:628–34.PubMedCrossRef Munzel T, Mollnau H, Hartmann M, Geiger C, Oelze M, Warnholtz A, et al. Effects of a nitrate-free interval on tolerance, vasoconstrictor sensitivity and vascular superoxide production. J Am Coll Cardiol. 2000;36:628–34.PubMedCrossRef
74.
Zurück zum Zitat Azevedo ER, Schofield AM, Kelly S, Parker JD. Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine. J Am Coll Cardiol. 2001;37:505–9.PubMedCrossRef Azevedo ER, Schofield AM, Kelly S, Parker JD. Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine. J Am Coll Cardiol. 2001;37:505–9.PubMedCrossRef
75.
Zurück zum Zitat Gori T. The puzzle of nitrate tolerance: pieces smaller than We thought? Circulation. 2002;106:2404–8.PubMedCrossRef Gori T. The puzzle of nitrate tolerance: pieces smaller than We thought? Circulation. 2002;106:2404–8.PubMedCrossRef
76.
Zurück zum Zitat La Rovere MT, Pinna GD, Hohnloser SH, Marcus FI, Mortara A, Nohara R, et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation. 2001;103:2072–7.PubMedCrossRef La Rovere MT, Pinna GD, Hohnloser SH, Marcus FI, Mortara A, Nohara R, et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation. 2001;103:2072–7.PubMedCrossRef
77.
Zurück zum Zitat Nitrates as an Integral Part of Optimal Medical Therapy and Cardiac Rehabilitation for Stable Angina: Review of Current Concepts and Therapeutics. 2015. pp. 1–9. Nitrates as an Integral Part of Optimal Medical Therapy and Cardiac Rehabilitation for Stable Angina: Review of Current Concepts and Therapeutics. 2015. pp. 1–9.
78.
Zurück zum Zitat Wei J, Wu T, Yang Q, Chen M, Ni J, Huang D. Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials. International journal of cardiology. Elsevier Ireland Ltd. 2011;146:4–12. Wei J, Wu T, Yang Q, Chen M, Ni J, Huang D. Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials. International journal of cardiology. Elsevier Ireland Ltd. 2011;146:4–12.
79.
Zurück zum Zitat Kimchi A, Lee G, Amsterdam E, Fujii K, Krieg P. Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris. Circulation 1983. Kimchi A, Lee G, Amsterdam E, Fujii K, Krieg P. Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris. Circulation 1983.
80.
Zurück zum Zitat Thadani, Thomas Wittig. A randomized, double-blind, placebo-controlled, crossover, dose-ranging multicenter study to determine the effect of sublingual nitroglycerin spray on exercise capacity in patients with chronic stable angina. Clinical Medicine Insights: Cardiology. 2012:6;87–95. Thadani, Thomas Wittig. A randomized, double-blind, placebo-controlled, crossover, dose-ranging multicenter study to determine the effect of sublingual nitroglycerin spray on exercise capacity in patients with chronic stable angina. Clinical Medicine Insights: Cardiology. 2012:6;87–95.
81.
Zurück zum Zitat Bassan MM, Rogel S. A comparison of the day-long antianginal effectiveness of nitroglycerin patches with that of three-times-daily isosorbide dinitrate: a double-blind study using dose titration. Eur Heart J. 1992;13(9):1265–70.PubMedCrossRef Bassan MM, Rogel S. A comparison of the day-long antianginal effectiveness of nitroglycerin patches with that of three-times-daily isosorbide dinitrate: a double-blind study using dose titration. Eur Heart J. 1992;13(9):1265–70.PubMedCrossRef
82.
Zurück zum Zitat Bassan MM. The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate. J Am Coll Cardiol. 1990:16(4);936–40. Bassan MM. The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate. J Am Coll Cardiol. 1990:16(4);936–40.
83.
Zurück zum Zitat Parker JO, Vankoughnett KA. Farrell B. The American Journal of Cardiology: Comparison of buccal nitroglycerin and oral isosorbide dinitrate for nitrate tolerance in stable angina pectoris. Am J cardiol. 1985;56(12):724–8. Parker JO, Vankoughnett KA. Farrell B. The American Journal of Cardiology: Comparison of buccal nitroglycerin and oral isosorbide dinitrate for nitrate tolerance in stable angina pectoris. Am J cardiol. 1985;56(12):724–8.
84.
Zurück zum Zitat Manyari DE, Smith ER, Spragg J. Isosorbide dinitrate and glyceryl trinitrate: demonstration of cross tolerance in the capacitance vessels. Am J Cardiol. 1985;55(8):927–31. Manyari DE, Smith ER, Spragg J. Isosorbide dinitrate and glyceryl trinitrate: demonstration of cross tolerance in the capacitance vessels. Am J Cardiol. 1985;55(8):927–31.
85.
Zurück zum Zitat Thadani U, Fung HL, Darke AC, Parker JO. Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy. AJC. 1982;49:411–9.CrossRef Thadani U, Fung HL, Darke AC, Parker JO. Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy. AJC. 1982;49:411–9.CrossRef
86.
Zurück zum Zitat Kardas P. Comparison of once daily versus twice daily oral nitrates in stable angina pectoris. Am J Cardiol. 2004;94:213–6.PubMedCrossRef Kardas P. Comparison of once daily versus twice daily oral nitrates in stable angina pectoris. Am J Cardiol. 2004;94:213–6.PubMedCrossRef
87.
Zurück zum Zitat Chrysant SG, Glasser SP, Bittar N, Shahidi FE, Danisa K, Ibrahim R, et al. Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris. AJC. 1993;72:1249–56.CrossRef Chrysant SG, Glasser SP, Bittar N, Shahidi FE, Danisa K, Ibrahim R, et al. Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris. AJC. 1993;72:1249–56.CrossRef
88.
Zurück zum Zitat Göller V, Clausen M, Henze E, Giesler M, Schmidt A, Kochs M, et al. Reduction of exercise-induced myocardial perfusion defects by isosorbide-5-nitrate: assessment using quantitative Tc-99m-MIBI-SPECT. Coron Artery Dis. 1995;6:245–9.PubMed Göller V, Clausen M, Henze E, Giesler M, Schmidt A, Kochs M, et al. Reduction of exercise-induced myocardial perfusion defects by isosorbide-5-nitrate: assessment using quantitative Tc-99m-MIBI-SPECT. Coron Artery Dis. 1995;6:245–9.PubMed
89.
Zurück zum Zitat Lewin HC, Hachamovitch R, Harris AG, Williams C, Schmidt J, Harris M, et al. Sustained reduction of exercise perfusion defect extent and severity with isosorbide mononitrate (Imdur) as demonstrated by means of technetium 99m sestamibi. J Nucl Cardiol. 2000;7:342–53.PubMedCrossRef Lewin HC, Hachamovitch R, Harris AG, Williams C, Schmidt J, Harris M, et al. Sustained reduction of exercise perfusion defect extent and severity with isosorbide mononitrate (Imdur) as demonstrated by means of technetium 99m sestamibi. J Nucl Cardiol. 2000;7:342–53.PubMedCrossRef
90.
Zurück zum Zitat Zwinderman AH, Cleophas TJ, van der Sluijs H, Niemeyer MG, Buunk BP, van der Wall EE. Comparison of 50-mg and 100-mg sustained-release isosorbide mononitrate in the treatment of stable angina pectoris: effects on quality-of-life indices. Dutch mononitrate quality of life (DUMQOL) study group. Angiology. 1999;50:963–9.PubMedCrossRef Zwinderman AH, Cleophas TJ, van der Sluijs H, Niemeyer MG, Buunk BP, van der Wall EE. Comparison of 50-mg and 100-mg sustained-release isosorbide mononitrate in the treatment of stable angina pectoris: effects on quality-of-life indices. Dutch mononitrate quality of life (DUMQOL) study group. Angiology. 1999;50:963–9.PubMedCrossRef
91.
Zurück zum Zitat Bogaert MG. Pharmacokinetics of organic nitrates in man: an overview. Eur Heart J. The Oxford University Press; 1988;9:33–7. Bogaert MG. Pharmacokinetics of organic nitrates in man: an overview. Eur Heart J. The Oxford University Press; 1988;9:33–7.
92.
Zurück zum Zitat Thadani U, Hamilton SF, Olson E, Anderson JL. Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris. Am J Cardiol. 1987;59:756–62.PubMedCrossRef Thadani U, Hamilton SF, Olson E, Anderson JL. Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris. Am J Cardiol. 1987;59:756–62.PubMedCrossRef
93.
Zurück zum Zitat Kaski JC, Hayward C, Mahida S, Baker S, Khong T. Tamargo J. OUP Oxford: Drugs in Cardiology; 2010. Kaski JC, Hayward C, Mahida S, Baker S, Khong T. Tamargo J. OUP Oxford: Drugs in Cardiology; 2010.
94.
Zurück zum Zitat Avanzas P, Kaski JC. Pharmacological treatment of chronic stable angina pectoris. Avanzas P, Kaski JC, editors. Cham: Springer; 2015.CrossRef Avanzas P, Kaski JC. Pharmacological treatment of chronic stable angina pectoris. Avanzas P, Kaski JC, editors. Cham: Springer; 2015.CrossRef
95.
Zurück zum Zitat Parker JO. Eccentric dosing with isosorbide-5-mononitrate in angina pectoris. AJC Elsevier. 1993;72:871–6.CrossRef Parker JO. Eccentric dosing with isosorbide-5-mononitrate in angina pectoris. AJC Elsevier. 1993;72:871–6.CrossRef
96.
Zurück zum Zitat Gori T, Burstein JM, Ahmed S, Miner SE, Al-Hesayen A, Kelly S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation. 2001;104:1119–23.PubMedCrossRef Gori T, Burstein JM, Ahmed S, Miner SE, Al-Hesayen A, Kelly S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation. 2001;104:1119–23.PubMedCrossRef
97.
Zurück zum Zitat Parker JO, Parker JD, Caldwell RW, Farrell B, Kaesemeyer WH. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol. 2002;39:1199–203.PubMedCrossRef Parker JO, Parker JD, Caldwell RW, Farrell B, Kaesemeyer WH. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol. 2002;39:1199–203.PubMedCrossRef
98.
Zurück zum Zitat Thadani U, Lipicky RJ. Short and long-acting oral nitrates for stable angina pectoris. Cardiovasc Drugs Ther. 1994;8:611–23.PubMedCrossRef Thadani U, Lipicky RJ. Short and long-acting oral nitrates for stable angina pectoris. Cardiovasc Drugs Ther. 1994;8:611–23.PubMedCrossRef
99.
Zurück zum Zitat Fox KM, Dargie HJ, Deanfield J, Maseri A. Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The transdermal nitrate investigators. Br Heart J. 1991;66:151–5.PubMedPubMedCentralCrossRef Fox KM, Dargie HJ, Deanfield J, Maseri A. Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The transdermal nitrate investigators. Br Heart J. 1991;66:151–5.PubMedPubMedCentralCrossRef
100.
Zurück zum Zitat Parker JO, Fung HL. Transdermal nitroglycerin in angina pectoris. AJC. 1984;54:471–6.CrossRef Parker JO, Fung HL. Transdermal nitroglycerin in angina pectoris. AJC. 1984;54:471–6.CrossRef
101.
Zurück zum Zitat Thadani U, Rodgers T. Side effects of using nitrates to treat angina. Expert Opin Drug Saf. 2006;5:667–74.PubMedCrossRef Thadani U, Rodgers T. Side effects of using nitrates to treat angina. Expert Opin Drug Saf. 2006;5:667–74.PubMedCrossRef
102.
Zurück zum Zitat Cleophas TJM, Niemeyer MG, van der Wall EE. Nitrate-induced headache in patients with stable angina pectoris: beneficial effect of starting on a low dosage. Am J Ther SAGE Publications. 1996;3:802–6.CrossRef Cleophas TJM, Niemeyer MG, van der Wall EE. Nitrate-induced headache in patients with stable angina pectoris: beneficial effect of starting on a low dosage. Am J Ther SAGE Publications. 1996;3:802–6.CrossRef
103.
Zurück zum Zitat Bagdy G, Riba P, Kecskeméti V, Chase D, Juhász G. Headache-type adverse effects of NO donors: vasodilation and beyond. Br J Pharmacol. 2010;160:20–35.PubMedPubMedCentralCrossRef Bagdy G, Riba P, Kecskeméti V, Chase D, Juhász G. Headache-type adverse effects of NO donors: vasodilation and beyond. Br J Pharmacol. 2010;160:20–35.PubMedPubMedCentralCrossRef
104.
Zurück zum Zitat Gomma DAH, Purcell HJ, Fox KM. Potassium Channel openers in myocardial ischaemia. Drugs Springer Int Publ. 2001;61:1705–10. Gomma DAH, Purcell HJ, Fox KM. Potassium Channel openers in myocardial ischaemia. Drugs Springer Int Publ. 2001;61:1705–10.
105.
Zurück zum Zitat Goldschmidt M, Landzberg BR, Frishman WH. Nicorandil: a potassium channel opening drug for treatment of ischemic heart disease. J Clin Pharmacol. 1996;36:559–72.PubMedCrossRef Goldschmidt M, Landzberg BR, Frishman WH. Nicorandil: a potassium channel opening drug for treatment of ischemic heart disease. J Clin Pharmacol. 1996;36:559–72.PubMedCrossRef
106.
Zurück zum Zitat Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. AJC. 1989;63:18J–24J.CrossRef Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. AJC. 1989;63:18J–24J.CrossRef
107.
Zurück zum Zitat Kukovetz WR, Holzmann S, Pöch G. Molecular mechanism of action of nicorandil. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S1–7.PubMedCrossRef Kukovetz WR, Holzmann S, Pöch G. Molecular mechanism of action of nicorandil. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S1–7.PubMedCrossRef
108.
Zurück zum Zitat Frydman A. Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S34–44.PubMedCrossRef Frydman A. Pharmacokinetic profile of nicorandil in humans: an overview. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S34–44.PubMedCrossRef
109.
Zurück zum Zitat Sumimoto K, Domae M, Yamanaka K, Nakao K, Hashimoto T, Kitamura K, et al. Actions of nicorandil on vascular smooth muscles. J Cardiovasc Pharmacol. 1987;10(Suppl 8):S66–75.PubMedCrossRef Sumimoto K, Domae M, Yamanaka K, Nakao K, Hashimoto T, Kitamura K, et al. Actions of nicorandil on vascular smooth muscles. J Cardiovasc Pharmacol. 1987;10(Suppl 8):S66–75.PubMedCrossRef
110.
Zurück zum Zitat Brodmann M, Lischnig U, Lueger A, Stark G, Pilger E. The effect of the K+ agonist nicorandil on peripheral vascular resistance. Int J Cardiol. 2006;111:49–52.PubMedCrossRef Brodmann M, Lischnig U, Lueger A, Stark G, Pilger E. The effect of the K+ agonist nicorandil on peripheral vascular resistance. Int J Cardiol. 2006;111:49–52.PubMedCrossRef
111.
Zurück zum Zitat Akai K, Wang Y, Sato K, Sekiguchi N, Sugimura A, Kumagai T, et al. Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels. J Cardiovasc Pharmacol. 1995;26:541–7.PubMedCrossRef Akai K, Wang Y, Sato K, Sekiguchi N, Sugimura A, Kumagai T, et al. Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels. J Cardiovasc Pharmacol. 1995;26:541–7.PubMedCrossRef
112.
Zurück zum Zitat Aizawa T, Ogasawara K, Kato K. Effects of nicorandil on coronary circulation in patients with ischemic heart disease: comparison with nitroglycerin. J Cardiovasc Pharmacol. 1987;10(Suppl 8):S123–9.PubMedCrossRef Aizawa T, Ogasawara K, Kato K. Effects of nicorandil on coronary circulation in patients with ischemic heart disease: comparison with nitroglycerin. J Cardiovasc Pharmacol. 1987;10(Suppl 8):S123–9.PubMedCrossRef
113.
Zurück zum Zitat Treese N, Erbel R, Meyer J. Acute hemodynamic effects of nicorandil in coronary artery disease. J Cardiovasc Pharmacol. 1992;20:S52.PubMedCrossRef Treese N, Erbel R, Meyer J. Acute hemodynamic effects of nicorandil in coronary artery disease. J Cardiovasc Pharmacol. 1992;20:S52.PubMedCrossRef
114.
Zurück zum Zitat Knight DC, Purcell H, Fox K. Potassium channel openers: clinical applications in ischemic heart disease—overview of clinical efficacy of nicorandil. Cardiovasc Drugs Ther Kluwer Acad Publishers; 1995;9:229–236. Knight DC, Purcell H, Fox K. Potassium channel openers: clinical applications in ischemic heart disease—overview of clinical efficacy of nicorandil. Cardiovasc Drugs Ther Kluwer Acad Publishers; 1995;9:229–236.
115.
Zurück zum Zitat Suryapranata H, Serruys PW, de Feyter PJ. Coronary vasodilatory action after a single dose of nicorandil. Am J Cardiol. 1988;61:292–7.PubMedCrossRef Suryapranata H, Serruys PW, de Feyter PJ. Coronary vasodilatory action after a single dose of nicorandil. Am J Cardiol. 1988;61:292–7.PubMedCrossRef
116.
Zurück zum Zitat Suryapranata H, MacLeod D. Nicorandil and cardiovascular performance in patients with coronary artery disease. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S45–51.PubMedCrossRef Suryapranata H, MacLeod D. Nicorandil and cardiovascular performance in patients with coronary artery disease. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S45–51.PubMedCrossRef
117.
Zurück zum Zitat Coltart DJ, Signy M. Acute hemodynamic effects of single-dose nicorandil in coronary artery disease. Am J Cardiol. 1989;63:J34–9.CrossRef Coltart DJ, Signy M. Acute hemodynamic effects of single-dose nicorandil in coronary artery disease. Am J Cardiol. 1989;63:J34–9.CrossRef
118.
Zurück zum Zitat Markham A, Plosker GL, Goa KL. Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects. Drugs. Springer Int Publ. 2000;60:955–74. Markham A, Plosker GL, Goa KL. Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects. Drugs. Springer Int Publ. 2000;60:955–74.
119.
Zurück zum Zitat Matsubara T, Minatoguchi S, Matsuo H, Hayakawa K, Segawa T, Matsuno Y, et al. Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease. J Am Coll Cardiol. 2000;35:345–51.PubMedCrossRef Matsubara T, Minatoguchi S, Matsuo H, Hayakawa K, Segawa T, Matsuno Y, et al. Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease. J Am Coll Cardiol. 2000;35:345–51.PubMedCrossRef
120.
Zurück zum Zitat Sekiya M, Sato M, Funada J, Ohtani T, Akutsu H, Watanabe K. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol. 2005;46:63–7.PubMedCrossRef Sekiya M, Sato M, Funada J, Ohtani T, Akutsu H, Watanabe K. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol. 2005;46:63–7.PubMedCrossRef
121.
Zurück zum Zitat Serizawa K-I, Yogo K, Aizawa K, Tashiro Y, Ishizuka N. Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats. Cardiovasc Diabetol. BioMed Central Ltd; 2011;10:105. Serizawa K-I, Yogo K, Aizawa K, Tashiro Y, Ishizuka N. Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats. Cardiovasc Diabetol. BioMed Central Ltd; 2011;10:105.
122.
Zurück zum Zitat Serizawa K-I, Yogo K, Aizawa K, Tashiro Y, Takahari Y, Sekine K, et al. Paclitaxel-induced endothelial dysfunction in living rats is prevented by nicorandil via reduction of oxidative stress. J Pharmacol Sci. 2012;119:349–58.PubMedCrossRef Serizawa K-I, Yogo K, Aizawa K, Tashiro Y, Takahari Y, Sekine K, et al. Paclitaxel-induced endothelial dysfunction in living rats is prevented by nicorandil via reduction of oxidative stress. J Pharmacol Sci. 2012;119:349–58.PubMedCrossRef
123.
Zurück zum Zitat Ishibashi Y, Takahashi N, Tokumaru A, Karino K, Sugamori T, Sakane T, et al. Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease. J Cardiovasc Pharmacol. 2008;51:311–6.PubMedCrossRef Ishibashi Y, Takahashi N, Tokumaru A, Karino K, Sugamori T, Sakane T, et al. Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease. J Cardiovasc Pharmacol. 2008;51:311–6.PubMedCrossRef
124.
Zurück zum Zitat Izumiya Y, Kojima S, Kojima S, Araki S, Usuku H, Matsubara J, et al. Atherosclerosis. Atherosclerosis Elsevier Ireland Ltd. 2011;214:415–21.CrossRef Izumiya Y, Kojima S, Kojima S, Araki S, Usuku H, Matsubara J, et al. Atherosclerosis. Atherosclerosis Elsevier Ireland Ltd. 2011;214:415–21.CrossRef
125.
Zurück zum Zitat Cavero I, Djellas Y, Guillon JM. Ischemic myocardial cell protection conferred by the opening of ATP-sensitive potassium channels. Cardiovasc Drugs Ther. 1995;9(Suppl 2):245–55.PubMedCrossRef Cavero I, Djellas Y, Guillon JM. Ischemic myocardial cell protection conferred by the opening of ATP-sensitive potassium channels. Cardiovasc Drugs Ther. 1995;9(Suppl 2):245–55.PubMedCrossRef
126.
Zurück zum Zitat Falase B, Easaw J, Youhana A. The role of nicorandil in the treatment of myocardial ischaemia. Expert Opin Pharmacother. 2001;2:845–56.PubMedCrossRef Falase B, Easaw J, Youhana A. The role of nicorandil in the treatment of myocardial ischaemia. Expert Opin Pharmacother. 2001;2:845–56.PubMedCrossRef
127.
Zurück zum Zitat Sato T, Sasaki N, O'Rourke B, Marbán E. Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels. JAC. 2000;35:514–8. Sato T, Sasaki N, O'Rourke B, Marbán E. Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels. JAC. 2000;35:514–8.
128.
Zurück zum Zitat Szewczyk A, Marbán E. Mitochondria: a new target for K channel openers? Trends Pharmacol Sci. 1999;20:157–61.PubMedCrossRef Szewczyk A, Marbán E. Mitochondria: a new target for K channel openers? Trends Pharmacol Sci. 1999;20:157–61.PubMedCrossRef
129.
Zurück zum Zitat Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM. Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res. 2002;55:534–43.PubMedCrossRef Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM. Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res. 2002;55:534–43.PubMedCrossRef
130.
Zurück zum Zitat Wu H, Ye M, Yang J, Ding J, Yang J, Dong W, et al. Nicorandil protects the heart from ischemia/reperfusion injury by attenuating endoplasmic reticulum response-induced apoptosis through PI3K/Akt signaling pathway. Cell Physiol Biochem Karger Publishers. 2015;35:2320–32.CrossRef Wu H, Ye M, Yang J, Ding J, Yang J, Dong W, et al. Nicorandil protects the heart from ischemia/reperfusion injury by attenuating endoplasmic reticulum response-induced apoptosis through PI3K/Akt signaling pathway. Cell Physiol Biochem Karger Publishers. 2015;35:2320–32.CrossRef
131.
Zurück zum Zitat IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the impact of nicorandil in angina (IONA) randomised trial. Lancet. 2002;359:1269–75.CrossRef IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the impact of nicorandil in angina (IONA) randomised trial. Lancet. 2002;359:1269–75.CrossRef
133.
Zurück zum Zitat Henderson RA, O'Flynn N, Guideline Development Group. Management of stable angina: summary of NICE guidance. Heart. BMJ Publ Group Ltd and Br Cardiovasc Soc; 2012. pp. 500–7. Henderson RA, O'Flynn N, Guideline Development Group. Management of stable angina: summary of NICE guidance. Heart. BMJ Publ Group Ltd and Br Cardiovasc Soc; 2012. pp. 500–7.
134.
Zurück zum Zitat Horinaka S, Yabe A, Yagi H, Ishimitsu T, Yamazaki T, Suzuki S, et al. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese coronary artery disease (JCAD) study. Circ J. 2010;74:503–9.PubMedCrossRef Horinaka S, Yabe A, Yagi H, Ishimitsu T, Yamazaki T, Suzuki S, et al. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese coronary artery disease (JCAD) study. Circ J. 2010;74:503–9.PubMedCrossRef
135.
Zurück zum Zitat Patel DJ, Purcell HJ, Fox KM. Cardioprotection by opening of the K(ATP) channel in unstable angina. Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. CESAR 2 investigation. Clinical European studies in angina and revascularization. Eur Heart J. 1999;20:51–7.PubMedCrossRef Patel DJ, Purcell HJ, Fox KM. Cardioprotection by opening of the K(ATP) channel in unstable angina. Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. CESAR 2 investigation. Clinical European studies in angina and revascularization. Eur Heart J. 1999;20:51–7.PubMedCrossRef
136.
Zurück zum Zitat Kinoshita M, Sakai K. Pharmacology and therapeutic effects of nicorandil. Cardiovasc Drugs Ther. 1990;4:1075–88.PubMedCrossRef Kinoshita M, Sakai K. Pharmacology and therapeutic effects of nicorandil. Cardiovasc Drugs Ther. 1990;4:1075–88.PubMedCrossRef
137.
Zurück zum Zitat Awata N, Azuma J, Sawamura A, Harada H, Hamaguchi T, Park S, et al. Efficacy of nicorandil on exercise performance in patients with stable effort angina: exercise echocardiography evaluation. Current therapeutic research. Elsevier. 1989;45:621–32. Awata N, Azuma J, Sawamura A, Harada H, Hamaguchi T, Park S, et al. Efficacy of nicorandil on exercise performance in patients with stable effort angina: exercise echocardiography evaluation. Current therapeutic research. Elsevier. 1989;45:621–32.
138.
Zurück zum Zitat Hiasa Y, Hamai K, Wada T, Aihara T, Bando M, Nakai Y, et al. Chronic effects of nicorandil on exercise tolerance in patients with stable effort angina pectoris. Tokushima J Exp Med. 1989;36:65–70.PubMed Hiasa Y, Hamai K, Wada T, Aihara T, Bando M, Nakai Y, et al. Chronic effects of nicorandil on exercise tolerance in patients with stable effort angina pectoris. Tokushima J Exp Med. 1989;36:65–70.PubMed
139.
Zurück zum Zitat Kinoshita M, Nishikawa S, Sawamura M, Yamaguchi S, Mitsunami K, Itoh M, et al. Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris. Am J Cardiol. 1986;58:733–8.PubMedCrossRef Kinoshita M, Nishikawa S, Sawamura M, Yamaguchi S, Mitsunami K, Itoh M, et al. Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris. Am J Cardiol. 1986;58:733–8.PubMedCrossRef
140.
Zurück zum Zitat Hayata N, Araki H, Nakamura M. Effects of nicorandil on exercise tolerance in patients with stable effort angina: a double-blind study. Am Heart J. 1986;112:1245–50.PubMedCrossRef Hayata N, Araki H, Nakamura M. Effects of nicorandil on exercise tolerance in patients with stable effort angina: a double-blind study. Am Heart J. 1986;112:1245–50.PubMedCrossRef
141.
Zurück zum Zitat Camm AJ, Maltz MB. A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris. Am J Cardiol Elsevier. 1989;63:J61–5.CrossRef Camm AJ, Maltz MB. A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris. Am J Cardiol Elsevier. 1989;63:J61–5.CrossRef
142.
Zurück zum Zitat Why HJ, Richardson PJ. A potassium channel opener as monotherapy in chronic stable angina pectoris: comparison with placebo. Eur Heart J. 1993;14 Suppl B:25–29. Why HJ, Richardson PJ. A potassium channel opener as monotherapy in chronic stable angina pectoris: comparison with placebo. Eur Heart J. 1993;14 Suppl B:25–29.
143.
Zurück zum Zitat Meany TB, Richardson P, Camm AJ, Coltart J, Griffith M, Maltz MB, et al. Exercise capacity after single and twice-daily doses of nicorandil in chronic stable angina pectoris. Am J Cardiol Elsevier. 1989;63:J66–70.CrossRef Meany TB, Richardson P, Camm AJ, Coltart J, Griffith M, Maltz MB, et al. Exercise capacity after single and twice-daily doses of nicorandil in chronic stable angina pectoris. Am J Cardiol Elsevier. 1989;63:J66–70.CrossRef
144.
Zurück zum Zitat Hanai Y, Mita M, Hishinuma S, Shoji M. Systematic review on the short-term efficacy and safety of nicorandil for stable angina pectoris in comparison with those of β-blockers, nitrates and calcium antagonists. Yakugaku Zasshi. 2010;130:1549–63.PubMedCrossRef Hanai Y, Mita M, Hishinuma S, Shoji M. Systematic review on the short-term efficacy and safety of nicorandil for stable angina pectoris in comparison with those of β-blockers, nitrates and calcium antagonists. Yakugaku Zasshi. 2010;130:1549–63.PubMedCrossRef
145.
Zurück zum Zitat Döring G. Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S74–81.PubMedCrossRef Döring G. Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S74–81.PubMedCrossRef
146.
Zurück zum Zitat Lai C, Onnis E, Solinas R, Orani E, Lai G, Cadeddu M, et al. A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate. Cardiologia. 1991;36:703–11.PubMed Lai C, Onnis E, Solinas R, Orani E, Lai G, Cadeddu M, et al. A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate. Cardiologia. 1991;36:703–11.PubMed
147.
Zurück zum Zitat Ulvenstam G, Diderholm E, Frithz G, Gudbrandsson T, Hedbäck B, Höglund C, et al. Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S67–73.PubMedCrossRef Ulvenstam G, Diderholm E, Frithz G, Gudbrandsson T, Hedbäck B, Höglund C, et al. Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S67–73.PubMedCrossRef
148.
Zurück zum Zitat Guermonprez JL, Blin P, Peterlongo F. A double-blind comparison of the long-term efficacy of a potassium channel opener and a calcium antagonist in stable angina pectoris. Eur Heart J. 1993;14 Suppl B:30–34. Guermonprez JL, Blin P, Peterlongo F. A double-blind comparison of the long-term efficacy of a potassium channel opener and a calcium antagonist in stable angina pectoris. Eur Heart J. 1993;14 Suppl B:30–34.
149.
Zurück zum Zitat Hughes LO, Rose EL, Lahiri A, Raftery EB. Comparison of nicorandil and atenolol in stable angina pectoris. Am J Cardiol. 1990;66:679–82.PubMedCrossRef Hughes LO, Rose EL, Lahiri A, Raftery EB. Comparison of nicorandil and atenolol in stable angina pectoris. Am J Cardiol. 1990;66:679–82.PubMedCrossRef
150.
Zurück zum Zitat Meeter K, Kelder JC, Tijssen JG, Bucx JJ, Henneman JA, Kerker JP, et al. Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S59–66.PubMed Meeter K, Kelder JC, Tijssen JG, Bucx JJ, Henneman JA, Kerker JP, et al. Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S59–66.PubMed
151.
Zurück zum Zitat Di Somma S, Liguori V, Petitto M, Carotenuto A, Bokor D, de Divitiis O, et al. A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. Cardiovasc Drugs Ther. 1993;7:119–23.PubMedCrossRef Di Somma S, Liguori V, Petitto M, Carotenuto A, Bokor D, de Divitiis O, et al. A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. Cardiovasc Drugs Ther. 1993;7:119–23.PubMedCrossRef
152.
Zurück zum Zitat Ciampricotti R, Schotborgh CE, De Kam PJ, van Herwaarden RH. A comparison of nicorandil with isosorbide mononitrate in elderly patients with stable coronary heart disease: The SNAPE study. Am Heart J. Mosby; 2000;139 Ciampricotti R, Schotborgh CE, De Kam PJ, van Herwaarden RH. A comparison of nicorandil with isosorbide mononitrate in elderly patients with stable coronary heart disease: The SNAPE study. Am Heart J. Mosby; 2000;139
153.
Zurück zum Zitat The SWAN Study. Comparison of the antiischaemic and antianginal effects of nicorandil and amlodipine in patients with symptomatic stable angina pectoris: the SWAN study. J Clin Basic Cardiol. 1999;2:213–7. The SWAN Study. Comparison of the antiischaemic and antianginal effects of nicorandil and amlodipine in patients with symptomatic stable angina pectoris: the SWAN study. J Clin Basic Cardiol. 1999;2:213–7.
154.
Zurück zum Zitat Frydman AM, Chapelle P, Diekmann H, Bruno R, Thebault JJ, Bouthier J, et al. Pharmacokinetics of nicorandil. Am J Cardiol. 1989;63:25J–33J.PubMedCrossRef Frydman AM, Chapelle P, Diekmann H, Bruno R, Thebault JJ, Bouthier J, et al. Pharmacokinetics of nicorandil. Am J Cardiol. 1989;63:25J–33J.PubMedCrossRef
155.
Zurück zum Zitat Wagner G. Selected issues from an overview on nicorandil: tolerance, duration of action, and long-term efficacy. J Cardiovasc Pharmacol. 1992;20:S86.PubMedCrossRef Wagner G. Selected issues from an overview on nicorandil: tolerance, duration of action, and long-term efficacy. J Cardiovasc Pharmacol. 1992;20:S86.PubMedCrossRef
156.
Zurück zum Zitat Kool MJ, Spek JJ, Struyker Boudier HA, Hoeks AP, Reneman RS, van Herwaarden RH, et al. Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers. Cardiovasc Drugs Ther Kluwer Acad Publishers. 1995;9:331–7.CrossRef Kool MJ, Spek JJ, Struyker Boudier HA, Hoeks AP, Reneman RS, van Herwaarden RH, et al. Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers. Cardiovasc Drugs Ther Kluwer Acad Publishers. 1995;9:331–7.CrossRef
157.
Zurück zum Zitat Roland E. Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. Eur Heart J. 1993;14 Suppl B:48–52. Roland E. Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. Eur Heart J. 1993;14 Suppl B:48–52.
158.
Zurück zum Zitat Witchitz S, Darmon JY. Nicorandil safety in the long-term treatment of coronary heart disease. Cardiovasc Drugs Ther. 1995;9(Suppl 2):237–43.PubMedCrossRef Witchitz S, Darmon JY. Nicorandil safety in the long-term treatment of coronary heart disease. Cardiovasc Drugs Ther. 1995;9(Suppl 2):237–43.PubMedCrossRef
159.
Zurück zum Zitat Agbo-Godeau S, Joly P, Lauret P, Szpirglas R, Szpirglas H. Association of major aphthous ulcers and nicorandil. Lancet. 1998;352:1598–9.PubMedCrossRef Agbo-Godeau S, Joly P, Lauret P, Szpirglas R, Szpirglas H. Association of major aphthous ulcers and nicorandil. Lancet. 1998;352:1598–9.PubMedCrossRef
160.
Zurück zum Zitat Watson A, Ozairi OA, Fraser A, Loudon M, O'Kelly T. Nicorandil associated anal ulceration. Lancet. 2002;360:546–7.PubMedCrossRef Watson A, Ozairi OA, Fraser A, Loudon M, O'Kelly T. Nicorandil associated anal ulceration. Lancet. 2002;360:546–7.PubMedCrossRef
161.
Zurück zum Zitat Dunn N, Freemantle S, Pearce G, Wilton LV, Mann RD. Safety profile of nicorandil–prescription-event monitoring (PEM) study. Pharmacoepidemiol Drug Saf. 1999;8:197–205.PubMedCrossRef Dunn N, Freemantle S, Pearce G, Wilton LV, Mann RD. Safety profile of nicorandil–prescription-event monitoring (PEM) study. Pharmacoepidemiol Drug Saf. 1999;8:197–205.PubMedCrossRef
162.
Zurück zum Zitat Reimann F, Ashcroft FM, Gribble FM. Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001;50:2253–9.PubMedCrossRef Reimann F, Ashcroft FM, Gribble FM. Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001;50:2253–9.PubMedCrossRef
163.
Zurück zum Zitat Hill JA, Feldman RL, Pepine CJ, Conti, CR. Randomized double-blind comparison of nifedipine and isosorbide dinitrate in patients with coronary arterial spasm. Am J Cardiol. 1982;49(2):431–8. Hill JA, Feldman RL, Pepine CJ, Conti, CR. Randomized double-blind comparison of nifedipine and isosorbide dinitrate in patients with coronary arterial spasm. Am J Cardiol. 1982;49(2):431–8.
164.
Zurück zum Zitat Lablanche JM, Bauters C, Leroy F, Bertrand ME. Prevention of coronary spasm by nicorandil: comparison with nifedipine. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S82–5.PubMedCrossRef Lablanche JM, Bauters C, Leroy F, Bertrand ME. Prevention of coronary spasm by nicorandil: comparison with nifedipine. J Cardiovasc Pharmacol. 1992;20(Suppl 3):S82–5.PubMedCrossRef
165.
Zurück zum Zitat Takahashi J, Nihei T, Takagi Y, Miyata S, Odaka Y, Tsunoda R, et al. Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association. Eur heart J. The Oxford University Press. 2015;36:228–37. Takahashi J, Nihei T, Takagi Y, Miyata S, Odaka Y, Tsunoda R, et al. Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association. Eur heart J. The Oxford University Press. 2015;36:228–37.
166.
Zurück zum Zitat Russo G, Di Franco A, Lamendola P, Tarzia P, Nerla R, Stazi A, et al. Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther. 2013;27:229–34.PubMedCrossRef Russo G, Di Franco A, Lamendola P, Tarzia P, Nerla R, Stazi A, et al. Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther. 2013;27:229–34.PubMedCrossRef
167.
Zurück zum Zitat Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol. 1995;25:807–14.PubMedCrossRef Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol. 1995;25:807–14.PubMedCrossRef
168.
Zurück zum Zitat Kaski JC, Valenzuela Garcia LF. Therapeutic options for the management of patients with cardiac syndrome X. Eur Heart J. 2001;22:283–93.PubMedCrossRef Kaski JC, Valenzuela Garcia LF. Therapeutic options for the management of patients with cardiac syndrome X. Eur Heart J. 2001;22:283–93.PubMedCrossRef
169.
Zurück zum Zitat Yamabe H, Namura H, Yano T, Fujita H, Kim S, Iwahashi M, et al. Effect of nicorandil on abnormal coronary flow reserve assessed by exercise 201Tl scintigraphy in patients with angina pectoris and nearly normal coronary arteriograms. Cardiovasc Drugs Ther. 1995;9:755–61.PubMedCrossRef Yamabe H, Namura H, Yano T, Fujita H, Kim S, Iwahashi M, et al. Effect of nicorandil on abnormal coronary flow reserve assessed by exercise 201Tl scintigraphy in patients with angina pectoris and nearly normal coronary arteriograms. Cardiovasc Drugs Ther. 1995;9:755–61.PubMedCrossRef
170.
Zurück zum Zitat Sadamatsu K, Inoue S, Tashiro H. Coronary slow flow phenomenon caused by contrast-induced microvascular spasm. Intern Med. 2007;46:1991–3.PubMedCrossRef Sadamatsu K, Inoue S, Tashiro H. Coronary slow flow phenomenon caused by contrast-induced microvascular spasm. Intern Med. 2007;46:1991–3.PubMedCrossRef
171.
Zurück zum Zitat Sadamatsu K, Tashiro H, Yoshida K, Shikada T, Iwamoto K, Morishige K, et al. Acute effects of isosorbide dinitrate and nicorandil on the coronary slow flow phenomenon. Am J Cardiovasc Drugs. 2010;10:203–8.PubMedCrossRef Sadamatsu K, Tashiro H, Yoshida K, Shikada T, Iwamoto K, Morishige K, et al. Acute effects of isosorbide dinitrate and nicorandil on the coronary slow flow phenomenon. Am J Cardiovasc Drugs. 2010;10:203–8.PubMedCrossRef
172.
Zurück zum Zitat Kiyooka T, Kobayashi Y, Ikari Y. A case of vasospastic angina in which the ergonovine provocation test with intracoronary isosorbide dinitrate and nicorandil was effective in the diagnosis of microvascular spasm. Cardiovasc Interv Ther. 2014;29(4):344–9. Kiyooka T, Kobayashi Y, Ikari Y. A case of vasospastic angina in which the ergonovine provocation test with intracoronary isosorbide dinitrate and nicorandil was effective in the diagnosis of microvascular spasm. Cardiovasc Interv Ther. 2014;29(4):344–9.
Metadaten
Titel
Vasodilator Therapy: Nitrates and Nicorandil
verfasst von
Jason M. Tarkin
Juan Carlos Kaski
Publikationsdatum
16.06.2016
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2016
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-016-6668-z

Weitere Artikel der Ausgabe 4/2016

Cardiovascular Drugs and Therapy 4/2016 Zur Ausgabe

Neu im Fachgebiet Kardiologie

Aggressive Blutdrucksenkung bei Risikopersonen?

12.07.2024 Arterielle Hypertonie Nachrichten

Geht es nach einer aktuellen chinesischen Studie, ist die Einstellung des systolischen Blutdrucks bei Risikopersonen auf Werte unter 120 mmHg mit weniger kardiovaskulären Ereignissen assoziiert als die Senkung auf Werte unter 140 mmHg.

Mehr Komplikationen beim akuten Koronarsyndrom ohne klassische Risikofaktoren

11.07.2024 Akutes Koronarsyndrom Nachrichten

Ein steigender Anteil von Personen mit akutem Koronarsyndrom (ACS) weist keine modifizierbaren Risikofaktoren auf. Wie sich das auf die Prognose auswirkt, wurde anhand eines australischen PCI-Registers untersucht. 

Taugen Risikoscores für Schlaganfall und Blutungen auch bei Krebskranken?

Britische Registerdaten sprechen dafür, dass sich die Blutungsrisikoprädiktion bei Personen mit Vorhofflimmern, die zugleich an Krebs leiden, nicht einfach aus Kohorten ohne Krebs übertragen lässt.

Bewusstsein während Reanimation – gibt es "typische" Fälle?

10.07.2024 Kardiopulmonale Reanimation Nachrichten

Australische Rettungsdienstdaten deuten darauf hin, dass sich Fälle, in denen eine laufende Reanimation Anzeichen von Bewusstsein induziert, von anderen Wiederbelebungsfällen unterscheiden könnten. Etwa mit Blick auf die Überlebenschancen.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.