Skip to main content
Erschienen in: Current Hypertension Reports 1/2013

01.02.2013 | Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

Opportunities for Targeting the Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Pathway in Hypertension

verfasst von: Rodrigo Araujo Fraga-Silva, Anderson Jose Ferreira, Robson Augusto Souza dos Santos

Erschienen in: Current Hypertension Reports | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

It is well known that the renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cardiovascular diseases. This is well illustrated by the great success of ACE inhibitors and angiotensin (Ang) II AT1 blockers in the treatment of hypertension and its complications. In the past decade, the classical concept of RAS orchestrated by a series of enzymatic reactions culminating in the linear generation and action of Ang II has expanded and become more complex. From the discoveries of new components such as the angiotensin converting enzyme 2 and the receptor Mas emerged a novel concept of dual opposite branches of the RAS: one vasoconstrictor and pro-hypertensive composed of ACE/Ang II/AT1; and other vasodilator and anti-hypertensive composed of ACE2/Ang-(1-7)/Mas. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular system and highlight the initiatives to develop potential therapeutic strategies based on this axis for treating hypertension.
Literatur
1.
Zurück zum Zitat Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol. 2002;89(2A):3A–9. discussion 10A.PubMedCrossRef Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol. 2002;89(2A):3A–9. discussion 10A.PubMedCrossRef
2.
Zurück zum Zitat Bader M. Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu Rev Pharmacol Toxicol. 2010;50:439–65.PubMedCrossRef Bader M. Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu Rev Pharmacol Toxicol. 2010;50:439–65.PubMedCrossRef
3.
Zurück zum Zitat Nicholls MG, Richards AM, Agarwal M. The importance of the renin-angiotensin system in cardiovascular disease. J Hum Hypertens. 1998;12(5):295–9.PubMedCrossRef Nicholls MG, Richards AM, Agarwal M. The importance of the renin-angiotensin system in cardiovascular disease. J Hum Hypertens. 1998;12(5):295–9.PubMedCrossRef
4.
Zurück zum Zitat Schiffrin EL. Vascular and cardiac benefits of angiotensin receptor blockers. Am J Med. 2002;113(5):409–18.PubMedCrossRef Schiffrin EL. Vascular and cardiac benefits of angiotensin receptor blockers. Am J Med. 2002;113(5):409–18.PubMedCrossRef
5.
Zurück zum Zitat Ma TK, et al. Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br J Pharmacol. 2010;160(6):1273–92.PubMedCrossRef Ma TK, et al. Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br J Pharmacol. 2010;160(6):1273–92.PubMedCrossRef
6.
Zurück zum Zitat Matsusaka T, Ichikawa I. Biological functions of angiotensin and its receptors. Annu Rev Physiol. 1997;59:395–412.PubMedCrossRef Matsusaka T, Ichikawa I. Biological functions of angiotensin and its receptors. Annu Rev Physiol. 1997;59:395–412.PubMedCrossRef
7.
Zurück zum Zitat Allen AM, Zhuo J, Mendelsohn FA. Localization and function of angiotensin AT1 receptors. Am J Hypertens. 2000;13(1 Pt 2):31S–8.PubMedCrossRef Allen AM, Zhuo J, Mendelsohn FA. Localization and function of angiotensin AT1 receptors. Am J Hypertens. 2000;13(1 Pt 2):31S–8.PubMedCrossRef
8.
Zurück zum Zitat de Gasparo M, et al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;52(3):415–72.PubMed de Gasparo M, et al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;52(3):415–72.PubMed
9.
Zurück zum Zitat Vickers C, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838–43.PubMedCrossRef Vickers C, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838–43.PubMedCrossRef
10.
Zurück zum Zitat Tipnis SR, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275(43):33238–43.PubMedCrossRef Tipnis SR, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275(43):33238–43.PubMedCrossRef
11.
Zurück zum Zitat Donoghue M, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1–9.PubMedCrossRef Donoghue M, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1–9.PubMedCrossRef
12.
Zurück zum Zitat Santos RA, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258–63.PubMedCrossRef Santos RA, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258–63.PubMedCrossRef
13.
Zurück zum Zitat Zisman LS, et al. Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate. Circulation. 2003;108(14):1679–81.PubMedCrossRef Zisman LS, et al. Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate. Circulation. 2003;108(14):1679–81.PubMedCrossRef
14.
Zurück zum Zitat Ferrario CM, et al. Counterregulatory actions of angiotensin-(1-7). Hypertension. 1997;30(3 Pt 2):535–41.PubMedCrossRef Ferrario CM, et al. Counterregulatory actions of angiotensin-(1-7). Hypertension. 1997;30(3 Pt 2):535–41.PubMedCrossRef
15.
Zurück zum Zitat Ferreira AJ, et al. Therapeutic implications of the vasoprotective axis of the renin-angiotensin system in cardiovascular diseases. Hypertension. 2010;55(2):207–13.PubMedCrossRef Ferreira AJ, et al. Therapeutic implications of the vasoprotective axis of the renin-angiotensin system in cardiovascular diseases. Hypertension. 2010;55(2):207–13.PubMedCrossRef
16.
Zurück zum Zitat Ferreira AJ, et al. New cardiovascular and pulmonary therapeutic strategies based on the angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis. Int J Hypertens. 2012;2012:147825.PubMed Ferreira AJ, et al. New cardiovascular and pulmonary therapeutic strategies based on the angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis. Int J Hypertens. 2012;2012:147825.PubMed
17.
Zurück zum Zitat Bindom SM, Lazartigues E. The sweeter side of ACE2: physiological evidence for a role in diabetes. Mol Cell Endocrinol. 2009;302(2):193–202.PubMedCrossRef Bindom SM, Lazartigues E. The sweeter side of ACE2: physiological evidence for a role in diabetes. Mol Cell Endocrinol. 2009;302(2):193–202.PubMedCrossRef
18.
Zurück zum Zitat Ferreira AJ, Santos RA. Cardiovascular actions of angiotensin-(1-7). Braz J Med Biol Res. 2005;38(4):499–507.PubMedCrossRef Ferreira AJ, Santos RA. Cardiovascular actions of angiotensin-(1-7). Braz J Med Biol Res. 2005;38(4):499–507.PubMedCrossRef
19.
Zurück zum Zitat Santos RA, Ferreira AJ, Simoes ESAC. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis. Exp Physiol. 2008;93(5):519–27.PubMedCrossRef Santos RA, Ferreira AJ, Simoes ESAC. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis. Exp Physiol. 2008;93(5):519–27.PubMedCrossRef
20.
Zurück zum Zitat Kokubu T, et al. Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation. Adv Exp Med Biol. 1979;120B:467–75.PubMed Kokubu T, et al. Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation. Adv Exp Med Biol. 1979;120B:467–75.PubMed
21.
Zurück zum Zitat Touyz RM, Berry C. Recent advances in angiotensin II signaling. Braz J Med Biol Res. 2002;35(9):1001–15.PubMedCrossRef Touyz RM, Berry C. Recent advances in angiotensin II signaling. Braz J Med Biol Res. 2002;35(9):1001–15.PubMedCrossRef
22.
Zurück zum Zitat Steckelings UM, Unger T. Angiotensin II type 2 receptor agonists–where should they be applied? Expert Opin Investig Drugs. 2012;21(6):763–6.PubMedCrossRef Steckelings UM, Unger T. Angiotensin II type 2 receptor agonists–where should they be applied? Expert Opin Investig Drugs. 2012;21(6):763–6.PubMedCrossRef
23.
Zurück zum Zitat Widdop RE, et al. AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension. 2002;40(4):516–20.PubMedCrossRef Widdop RE, et al. AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension. 2002;40(4):516–20.PubMedCrossRef
24.
Zurück zum Zitat Savoia C, et al. Angiotensin type 2 receptor in hypertensive cardiovascular disease. Curr Opin Nephrol Hypertens. 2011;20(2):125–32.PubMedCrossRef Savoia C, et al. Angiotensin type 2 receptor in hypertensive cardiovascular disease. Curr Opin Nephrol Hypertens. 2011;20(2):125–32.PubMedCrossRef
25.
Zurück zum Zitat Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med. 2008;264(3):224–36.PubMedCrossRef Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med. 2008;264(3):224–36.PubMedCrossRef
26.
Zurück zum Zitat Bosnyak S, et al. Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin Sci (Lond). 2011;121(7):297–303. Bosnyak S, et al. Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin Sci (Lond). 2011;121(7):297–303.
27.
Zurück zum Zitat Albiston AL, et al. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 2001;276(52):48623–6.PubMedCrossRef Albiston AL, et al. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 2001;276(52):48623–6.PubMedCrossRef
28.
29.
Zurück zum Zitat Schiavone MT, et al. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc Natl Acad Sci U S A. 1988;85(11):4095–8.PubMedCrossRef Schiavone MT, et al. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc Natl Acad Sci U S A. 1988;85(11):4095–8.PubMedCrossRef
30.
Zurück zum Zitat Rice GI, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383(Pt 1):45–51.PubMed Rice GI, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383(Pt 1):45–51.PubMed
31.
Zurück zum Zitat Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27(3 Pt 2):523–8.PubMedCrossRef Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27(3 Pt 2):523–8.PubMedCrossRef
32.
Zurück zum Zitat Sampaio WO, Nascimento AA, Santos RA. Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats. Am J Physiol Heart Circ Physiol. 2003;284(6):H1985–94.PubMed Sampaio WO, Nascimento AA, Santos RA. Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats. Am J Physiol Heart Circ Physiol. 2003;284(6):H1985–94.PubMed
33.
Zurück zum Zitat Freeman EJ, et al. Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension. 1996;28(1):104–8.PubMedCrossRef Freeman EJ, et al. Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension. 1996;28(1):104–8.PubMedCrossRef
34.
Zurück zum Zitat Gava E, et al. Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart. Regul Pept. 2012;175(1–3):30–42.PubMedCrossRef Gava E, et al. Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart. Regul Pept. 2012;175(1–3):30–42.PubMedCrossRef
35.
Zurück zum Zitat Xu P, et al. Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension. 2008;51(2):574–80.PubMedCrossRef Xu P, et al. Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension. 2008;51(2):574–80.PubMedCrossRef
36.
Zurück zum Zitat Rabelo LA, Alenina N, Bader M. ACE2-angiotensin-(1-7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res. 2011;34(2):154–60.PubMedCrossRef Rabelo LA, Alenina N, Bader M. ACE2-angiotensin-(1-7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res. 2011;34(2):154–60.PubMedCrossRef
37.
Zurück zum Zitat Fraga-Silva RA, et al. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008;14(1–2):28–35.PubMed Fraga-Silva RA, et al. The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 2008;14(1–2):28–35.PubMed
38.
Zurück zum Zitat •• Fraga-Silva RA, et al. An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect. Clinics (Sao Paulo). 2011;66(5):837–41. This work shows that the oral formulations Ang-(1-7)-CyD produces biological activity through increasing Ang-(1-7) plasma level and in a Mas-dependent manner.CrossRef •• Fraga-Silva RA, et al. An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect. Clinics (Sao Paulo). 2011;66(5):837–41. This work shows that the oral formulations Ang-(1-7)-CyD produces biological activity through increasing Ang-(1-7) plasma level and in a Mas-dependent manner.CrossRef
39.
Zurück zum Zitat Fraga-Silva RA, et al. The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis: a potential target for treating thrombotic diseases. Thromb Haemost. 2012;108(6). doi:10.1160/TH12-06-0396. Fraga-Silva RA, et al. The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis: a potential target for treating thrombotic diseases. Thromb Haemost. 2012;108(6). doi:10.​1160/​TH12-06-0396.
40.
Zurück zum Zitat Santos RA, Campagnole-Santos MJ, Andrade SP. Angiotensin-(1-7): an update. Regul Pept. 2000;91(1–3):45–62.PubMedCrossRef Santos RA, Campagnole-Santos MJ, Andrade SP. Angiotensin-(1-7): an update. Regul Pept. 2000;91(1–3):45–62.PubMedCrossRef
41.
Zurück zum Zitat Silva DM, et al. Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats. Peptides. 2007;28(3):702–7.PubMedCrossRef Silva DM, et al. Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats. Peptides. 2007;28(3):702–7.PubMedCrossRef
42.
Zurück zum Zitat •• Verano-Braga T, et al. Time-resolved quantitative phosphoproteomics: new insights into angiotensin-(1-7) signaling networks in human endothelial cells. J Proteome Res. 2012;11(6):3370–81. This study provides new concepts and new understanding of the Ang-(1−7) signal transduction, shedding light on the mechanisms underlying Mas activation. •• Verano-Braga T, et al. Time-resolved quantitative phosphoproteomics: new insights into angiotensin-(1-7) signaling networks in human endothelial cells. J Proteome Res. 2012;11(6):3370–81. This study provides new concepts and new understanding of the Ang-(17) signal transduction, shedding light on the mechanisms underlying Mas activation.
43.
Zurück zum Zitat Heitsch H, et al. Angiotensin-(1-7)-stimulated nitric oxide and superoxide release from endothelial cells. Hypertension. 2001;37(1):72–6.PubMedCrossRef Heitsch H, et al. Angiotensin-(1-7)-stimulated nitric oxide and superoxide release from endothelial cells. Hypertension. 2001;37(1):72–6.PubMedCrossRef
44.
Zurück zum Zitat Sampaio WO, et al. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension. 2007;49(1):185–92.PubMedCrossRef Sampaio WO, et al. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension. 2007;49(1):185–92.PubMedCrossRef
45.
Zurück zum Zitat Sampaio WO, et al. Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50(6):1093–8.PubMedCrossRef Sampaio WO, et al. Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50(6):1093–8.PubMedCrossRef
46.
Zurück zum Zitat Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005;24(50):7410–25.PubMedCrossRef Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005;24(50):7410–25.PubMedCrossRef
47.
Zurück zum Zitat Zhao Y, Wang Y, Zhu WG. Applications of post-translational modifications of FoxO family proteins in biological functions. J Mol Cell Biol. 2011;3(5):276–82.PubMedCrossRef Zhao Y, Wang Y, Zhu WG. Applications of post-translational modifications of FoxO family proteins in biological functions. J Mol Cell Biol. 2011;3(5):276–82.PubMedCrossRef
48.
Zurück zum Zitat Brunet A, et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell. 1999;96(6):857–68.PubMedCrossRef Brunet A, et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell. 1999;96(6):857–68.PubMedCrossRef
49.
Zurück zum Zitat Zhu Z, et al. Angiotensin-(1-7) inhibits angiotensin II-induced signal transduction. J Cardiovasc Pharmacol. 2002;40(5):693–700.PubMedCrossRef Zhu Z, et al. Angiotensin-(1-7) inhibits angiotensin II-induced signal transduction. J Cardiovasc Pharmacol. 2002;40(5):693–700.PubMedCrossRef
50.
Zurück zum Zitat Giani JF, et al. Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity. Exp Physiol. 2008;93(5):570–8.PubMed Giani JF, et al. Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity. Exp Physiol. 2008;93(5):570–8.PubMed
51.
Zurück zum Zitat Mercure C, et al. Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart. Circ Res. 2008;103(11):1319–26.PubMedCrossRef Mercure C, et al. Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart. Circ Res. 2008;103(11):1319–26.PubMedCrossRef
52.
Zurück zum Zitat Gomes ER, et al. Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway. Hypertension. 2010;55(1):153–60.PubMedCrossRef Gomes ER, et al. Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway. Hypertension. 2010;55(1):153–60.PubMedCrossRef
53.
Zurück zum Zitat Iyer SN, Ferrario CM, Chappell MC. Angiotensin-(1-7) contributes to the antihypertensive effects of blockade of the renin-angiotensin system. Hypertension. 1998;31(1 Pt 2):356–61.PubMedCrossRef Iyer SN, Ferrario CM, Chappell MC. Angiotensin-(1-7) contributes to the antihypertensive effects of blockade of the renin-angiotensin system. Hypertension. 1998;31(1 Pt 2):356–61.PubMedCrossRef
54.
Zurück zum Zitat Iyer SN, et al. Vasodepressor actions of angiotensin-(1-7) unmasked during combined treatment with lisinopril and losartan. Hypertension. 1998;31(2):699–705.PubMedCrossRef Iyer SN, et al. Vasodepressor actions of angiotensin-(1-7) unmasked during combined treatment with lisinopril and losartan. Hypertension. 1998;31(2):699–705.PubMedCrossRef
55.
Zurück zum Zitat Collister JP, Hendel MD. The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats. J Renin Angiotensin Aldosterone Syst. 2003;4(3):176–9.PubMedCrossRef Collister JP, Hendel MD. The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats. J Renin Angiotensin Aldosterone Syst. 2003;4(3):176–9.PubMedCrossRef
56.
Zurück zum Zitat Kucharewicz I, et al. Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7). Hypertension. 2002;40(5):774–9.PubMedCrossRef Kucharewicz I, et al. Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7). Hypertension. 2002;40(5):774–9.PubMedCrossRef
57.
Zurück zum Zitat Yamada K, et al. Converting enzyme determines plasma clearance of angiotensin-(1-7). Hypertension. 1998;32(3):496–502.PubMedCrossRef Yamada K, et al. Converting enzyme determines plasma clearance of angiotensin-(1-7). Hypertension. 1998;32(3):496–502.PubMedCrossRef
58.
Zurück zum Zitat Wiemer G, et al. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium. Hypertension. 2002;40(6):847–52.PubMedCrossRef Wiemer G, et al. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium. Hypertension. 2002;40(6):847–52.PubMedCrossRef
59.
Zurück zum Zitat Santos RA, Ferreira AJ. Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor agonist. Cardiovasc Drug Rev. 2006;24(3–4):239–46.PubMedCrossRef Santos RA, Ferreira AJ. Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor agonist. Cardiovasc Drug Rev. 2006;24(3–4):239–46.PubMedCrossRef
61.
Zurück zum Zitat Pinheiro SV, et al. Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney. Hypertension. 2004;44(4):490–6.PubMedCrossRef Pinheiro SV, et al. Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney. Hypertension. 2004;44(4):490–6.PubMedCrossRef
62.
Zurück zum Zitat Lemos VS, et al. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 2005;46(3):274–9.PubMedCrossRef Lemos VS, et al. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 2005;46(3):274–9.PubMedCrossRef
63.
Zurück zum Zitat Ferreira AJ, et al. The nonpeptide angiotensin-(1-7) receptor Mas agonist AVE-0991 attenuates heart failure induced by myocardial infarction. Am J Physiol Heart Circ Physiol. 2007;292(2):H1113–9.PubMedCrossRef Ferreira AJ, et al. The nonpeptide angiotensin-(1-7) receptor Mas agonist AVE-0991 attenuates heart failure induced by myocardial infarction. Am J Physiol Heart Circ Physiol. 2007;292(2):H1113–9.PubMedCrossRef
64.
Zurück zum Zitat Ferreira AJ, et al. Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991. Life Sci. 2007;81(11):916–23.PubMedCrossRef Ferreira AJ, et al. Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991. Life Sci. 2007;81(11):916–23.PubMedCrossRef
65.
Zurück zum Zitat Benter IF, et al. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006;290(2):H684–91.PubMedCrossRef Benter IF, et al. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006;290(2):H684–91.PubMedCrossRef
66.
Zurück zum Zitat Faria-Silva R, Duarte FV, Santos RA. Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats. Hypertension. 2005;46(4):948–52.PubMedCrossRef Faria-Silva R, Duarte FV, Santos RA. Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats. Hypertension. 2005;46(4):948–52.PubMedCrossRef
67.
Zurück zum Zitat Carvalho MB, et al. Evidence for Mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats. Hypertension. 2007;50(4):762–7.PubMedCrossRef Carvalho MB, et al. Evidence for Mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats. Hypertension. 2007;50(4):762–7.PubMedCrossRef
68.
Zurück zum Zitat Singh Y, Singh K, Sharma PL. Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA-salt-induced hypertension in rats. Mol Cell Biochem. 2012. doi:10.1007/s11010-012-1489-2. Singh Y, Singh K, Sharma PL. Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA-salt-induced hypertension in rats. Mol Cell Biochem. 2012. doi:10.​1007/​s11010-012-1489-2.
69.
Zurück zum Zitat Shemesh R, et al. Discovery and validation of novel peptide agonists for G-protein-coupled receptors. J Biol Chem. 2008;283(50):34643–9.PubMedCrossRef Shemesh R, et al. Discovery and validation of novel peptide agonists for G-protein-coupled receptors. J Biol Chem. 2008;283(50):34643–9.PubMedCrossRef
70.
Zurück zum Zitat • Savergnini SQ, et al. Vascular relaxation, antihypertensive effect, and cardioprotection of a novel peptide agonist of the MAS receptor. Hypertension. 2010;56(1):112–20. This recent study was the first indicating that the novel Mas agonist, CGEN-856S, might have a therapeutic value, since it induces vasorelaxation, antihypertensive, and cardioprotective effects.PubMedCrossRef • Savergnini SQ, et al. Vascular relaxation, antihypertensive effect, and cardioprotection of a novel peptide agonist of the MAS receptor. Hypertension. 2010;56(1):112–20. This recent study was the first indicating that the novel Mas agonist, CGEN-856S, might have a therapeutic value, since it induces vasorelaxation, antihypertensive, and cardioprotective effects.PubMedCrossRef
71.
Zurück zum Zitat Lula I, et al. Study of angiotensin-(1-7) vasoactive peptide and its beta-cyclodextrin inclusion complexes: complete sequence-specific NMR assignments and structural studies. Peptides. 2007;28(11):2199–210.PubMedCrossRef Lula I, et al. Study of angiotensin-(1-7) vasoactive peptide and its beta-cyclodextrin inclusion complexes: complete sequence-specific NMR assignments and structural studies. Peptides. 2007;28(11):2199–210.PubMedCrossRef
72.
Zurück zum Zitat Uekama K. Design and evaluation of cyclodextrin-based drug formulation. Chem Pharm Bull (Tokyo). 2004;52(8):900–15.CrossRef Uekama K. Design and evaluation of cyclodextrin-based drug formulation. Chem Pharm Bull (Tokyo). 2004;52(8):900–15.CrossRef
73.
Zurück zum Zitat •• Marques FD, et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats. Hypertension. 2011;57(3):477–83. This work is the first showing the cardioprotective effects of Ang-(1-7) formulation, Ang-(1-7)-CyD.PubMedCrossRef •• Marques FD, et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats. Hypertension. 2011;57(3):477–83. This work is the first showing the cardioprotective effects of Ang-(1-7) formulation, Ang-(1-7)-CyD.PubMedCrossRef
74.
Zurück zum Zitat • Kluskens LD, et al. Angiotensin-(1-7) with thioether bridge: an angiotensin-converting enzyme-resistant, potent angiotensin-(1-7) analog. J Pharmacol Exp Ther. 2009;328(3):849–54. In this work it was developed the cyclized Ang-(1-7) compound which was proposed as an excellent method to render more resistance against proteolytic breakdown but preserving its activity.PubMedCrossRef • Kluskens LD, et al. Angiotensin-(1-7) with thioether bridge: an angiotensin-converting enzyme-resistant, potent angiotensin-(1-7) analog. J Pharmacol Exp Ther. 2009;328(3):849–54. In this work it was developed the cyclized Ang-(1-7) compound which was proposed as an excellent method to render more resistance against proteolytic breakdown but preserving its activity.PubMedCrossRef
75.
Zurück zum Zitat Durik M, et al. The effect of the thioether-bridged, stabilized Angiotensin-(1-7) analogue cyclic ang-(1-7) on cardiac remodeling and endothelial function in rats with myocardial infarction. Int J Hypertens. 2012;2012:536426.PubMed Durik M, et al. The effect of the thioether-bridged, stabilized Angiotensin-(1-7) analogue cyclic ang-(1-7) on cardiac remodeling and endothelial function in rats with myocardial infarction. Int J Hypertens. 2012;2012:536426.PubMed
76.
Zurück zum Zitat Hernandez Prada JA, et al. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension. 2008;51(5):1312–7.PubMedCrossRef Hernandez Prada JA, et al. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension. 2008;51(5):1312–7.PubMedCrossRef
77.
Zurück zum Zitat Ferreira AJ, et al. Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases. Exp Physiol. 2011;96(3):287–94.PubMedCrossRef Ferreira AJ, et al. Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases. Exp Physiol. 2011;96(3):287–94.PubMedCrossRef
78.
Zurück zum Zitat Ferreira AJ, et al. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179(11):1048–54.PubMedCrossRef Ferreira AJ, et al. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179(11):1048–54.PubMedCrossRef
79.
Zurück zum Zitat Fraga-Silva RA, et al. ACE2 activation promotes antithrombotic activity. Mol Med. 2010;16(5–6):210–5.PubMed Fraga-Silva RA, et al. ACE2 activation promotes antithrombotic activity. Mol Med. 2010;16(5–6):210–5.PubMed
80.
Zurück zum Zitat Murca TM, et al. Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction. Regul Pept. 2012;177(1–3):107–15.PubMedCrossRef Murca TM, et al. Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction. Regul Pept. 2012;177(1–3):107–15.PubMedCrossRef
81.
Zurück zum Zitat Murca TM, et al. Chronic activation of endogenous angiotensin-converting enzyme 2 protects diabetic rats from cardiovascular autonomic dysfunction. Exp Physiol. 2012;97(6):699–709.PubMed Murca TM, et al. Chronic activation of endogenous angiotensin-converting enzyme 2 protects diabetic rats from cardiovascular autonomic dysfunction. Exp Physiol. 2012;97(6):699–709.PubMed
82.
Zurück zum Zitat Sasaki S, et al. Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and patients with essential hypertension. Hypertension. 2001;38(1):90–4.PubMedCrossRef Sasaki S, et al. Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and patients with essential hypertension. Hypertension. 2001;38(1):90–4.PubMedCrossRef
83.
Zurück zum Zitat Davie AP, McMurray JJ. Effect of angiotensin-(1-7) and bradykinin in patients with heart failure treated with an ACE inhibitor. Hypertension. 1999;34(3):457–60.PubMedCrossRef Davie AP, McMurray JJ. Effect of angiotensin-(1-7) and bradykinin in patients with heart failure treated with an ACE inhibitor. Hypertension. 1999;34(3):457–60.PubMedCrossRef
Metadaten
Titel
Opportunities for Targeting the Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Pathway in Hypertension
verfasst von
Rodrigo Araujo Fraga-Silva
Anderson Jose Ferreira
Robson Augusto Souza dos Santos
Publikationsdatum
01.02.2013
Verlag
Current Science Inc.
Erschienen in
Current Hypertension Reports / Ausgabe 1/2013
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-012-0324-1

Weitere Artikel der Ausgabe 1/2013

Current Hypertension Reports 1/2013 Zur Ausgabe

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

Direct Activation of ENaC by Angiotensin II: Recent Advances and New Insights

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

Update on the Angiotensin AT2 Receptor

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

The Role of Type 1 Angiotensin Receptors on T Lymphocytes in Cardiovascular and Renal Diseases

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

The “His and Hers” of the Renin-Angiotensin System

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

Treatment of Arterial Remodeling in Essential Hypertension

Hypertension and the Kidney (RM Carey and A Mimran, Section Editors)

The Renin Angiotensin Aldosterone System and Insulin Resistance in Humans

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

10.05.2024 Hypercholesterinämie Nachrichten

Patienten mit Arteriosklerose-bedingten kardiovaskulären Erkrankungen, die trotz Statineinnahme zu hohe Triglyzeridspiegel haben, profitieren von einer Behandlung mit Icosapent-Ethyl, und zwar unabhängig vom individuellen Risikoprofil.

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

In den USA ist erstmals eine bioresorbierbare Gefäßstütze – auch Scaffold genannt – zur Rekanalisation infrapoplitealer Arterien bei schwerer PAVK zugelassen worden. Das markiert einen Wendepunkt in der Geschichte dieser speziellen Gefäßstützen.

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

10.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Mit Capsaicin-Pflastern steht eine neue innovative Therapie bei schmerzhafter diabetischer Polyneuropathie zur Verfügung. Bei therapierefraktären Schmerzen stellt die Hochfrequenz-Rückenmarkstimulation eine adäquate Option dar.

Update Innere Medizin

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