Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Hypertension Reports
Erschienen in: Current Hypertension Reports 5/2013

01.10.2013 | Hypertension Management and Antihypertensive Drugs (HM Siragy and B Waeber, Section Editors)

Endothelin Antagonism and Its Role in the Treatment of Hypertension

verfasst von: Rebecca C. Moorhouse, David J. Webb, David C. Kluth, Neeraj Dhaun

Erschienen in: Current Hypertension Reports | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Hypertension contributes greatly to global disease burden and in many patients current treatments do not adequately control blood pressure (BP). Endothelin-1 (ET-1) is a potent vasoconstrictor that is implicated in the pathogenesis of hypertension, including the hypertension that is often associated with chronic kidney disease (CKD) and the metabolic syndrome. ET receptor antagonists, currently licensed for the treatment of pulmonary arterial hypertension and scleroderma-related digital ulcers, are being investigated for the treatment of hypertension. Clinical trials have addressed the use of ET receptor antagonists as monotherapy in primary hypertension, as an add-on therapy in resistant hypertension and in CKD. This review will evaluate the current evidence regarding the therapeutic potential of ET receptor antagonists in hypertension, as well as highlighting important issues that still need to be addressed.
Literatur
1.
Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–60.PubMedCrossRef
2.
Myat A, Redwood SR, Qureshi AC, et al. Resistant hypertension. Br Med J. 2012;345:7.
3.
4.
5.
Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial-cells. Nature. 1988;332:411–5.PubMedCrossRef
6.
Inoue A, Yanagisawa M, Kimura S et al. The human endothelin family - 3 structurally and pharmacologically distinct isopeptides predicted by 3 separate genes. PNAS 1989,86.
7.
Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet. 1994;344:852–4.PubMedCrossRef
8.
Komuro I, Kurihara H, Sugiyama T, et al. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth-muscle cells. FEBS Lett. 1988;238:249–52.PubMedCrossRef
9.
Dawes KE, Cambrey AD, Campa JS, et al. Changes in collagen metabolism in response to endothelin-1: Evidence for fibroblast heterogeneity. Int J Biochem Cell Biol. 1996;28:229–38.PubMedCrossRef
10.
Halcox JPJ, Nour KRA, Zalos G, Quyyumi AA. Coronary vasodilation and improvement in endothelial dysfunction with endothelin ETA receptor blockade. Circ Res. 2001;89:969–76.PubMedCrossRef
11.
Vuurmans TJL, Boer P, Koomans HA. Effects of endothelin-1 and endothelin-1 receptor blockade on cardiac output, aortic pressure, and pulse wave velocity in humans. Hypertension. 2003;41:1253–8.PubMedCrossRef
12.
Shohet RV, Kisanuki YY, Zhao XS, et al. Mice with cardiomyocyte-specific disruption of the endothelin-1 gene are resistant to hyperthyroid cardiac hypertrophy. PNAS. 2004;101:2088–93.PubMedCrossRef
13.
Attina T, Camidge R, Newby DE, Webb DJ. Endothelin antagonism in pulmonary hypertension, heart failure, and beyond. Heart. 2005;91:825–31.PubMedCrossRef
14.
Wagner OF, Christ G, Wojta J, et al. Polar secretion of endothelin-1 by cultured endothelial-cells. J Biol Chem. 1992;267:16066–8.PubMed
15.
Arai H, Hori S, Aramori I et al. Cloning and expression of a cDNA-encoding an endothelin receptor. Nature 1990,348.
16.
Sakamoto A, Yanagisawa M, Sakurai T et al. Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochem Biophys Res Comm 1991,178.
17.
Davenport AP, Oreilly G, Kuc RE. Endothelin ETA and ETB messenger-rna and receptors expressed by smooth-muscle in the human vasculature - majority of the ETA sub-type. Br J Pharmacol. 1995;114:1110–6.PubMedCrossRef
18.
Karet FE, Kuc RE, Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int. 1993;44:36–42.PubMedCrossRef
19.
Herrera M, Garvin JL. Endothelin stimulates endothelial nitric oxide synthase expression in the thick ascending limb. Am J Physiol. 2004;287:F231–5.
20.
Johnstrom P, Fryer TD, Richards HK, et al. Positron emission tomography using F-18-labelled endothelin-1 reveals prevention of binding to cardiac receptors owing to tissue-specific clearance by ETB receptors in vivo. Br J Pharmacol. 2005;144:115–22.PubMedCrossRef
21.
Maguire JJ, Kuc RE, Davenport AP. Defining the affinity and receptor sub-type selectivity of four classes of endothelin antagonists in clinically relevant human cardiovascular tissues. Life Sci. 2012;91:681–6.PubMedCrossRef
22.
Goddard J, Webb DJ. Endothelin antagonists and hypertension: A question of dose? Hypertension. 2002;40:E1–2.PubMedCrossRef
23.
Schiffrin EL. Vascular endothelin in hypertension. Vasc Pharmacol 2005,43.
24.
Mortensen LH, Pawloski CM, Kanagy NL, Fink GD. Chronic hypertension produced by infusion of endothelin in rats. Hypertension. 1990;15:729–33.PubMedCrossRef
25.
Pollock DM, Pollock JS. Evidence for endothelin involvement in the response to high salt. Am J Physiol. 2001;281:F144–50.
26.
Mortensen LH, Fink GD. Salt-dependency of endothelin-induced, chronic hypertension in conscious rats. Hypertension. 1992;19:549–54.PubMedCrossRef
27.
Moreau P. Endothelin in hypertension: A role for receptor antagonists? Cardiovasc Res. 1998;39:534–42.PubMedCrossRef
28.
Saito Y, Nakao K, Mukoyama M, Imura H. Increased plasma endothelin level in patients with essential-hypertension. New Engl J Med 1990,322.
29.
Cody RJ, Haas GJ, Binkley PF et al. Plasma endothelin correlates with the extent of pulmonary-hypertension in patients with chronic congestive-heart-failure. Circulation 1992,85.
30.
Davenport AP, Ashby MJ, Easton P, et al. A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma - comparison of levels in patients with essential-hypertension and normotensive control subjects. Clin Sci. 1990;78:261–4.PubMed
31.
Schiffrin EL, Thibault G. Plasma endothelin in human essential-hypertension. Am J Hyper. 1991;4:303–8.
32.
Fukuroda T, Fujikawa T, Ozaki S et al. Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun 1994,199.
33.
Cardillo C, Kilcoyne CM, Waclawiw M, et al. Role of endothelin in the increased vascular tone of patients with essential hypertension. Hypertension. 1999;33:753–8.PubMedCrossRef
34.
Martin P, Ninio D, Krum H. Effect of endothelin blockade on basal and stimulated forearm blood flow in patients with essential hypertension. Hypertension. 2002;39:821–4.PubMedCrossRef
35.
Krum H, Viskoper RJ, Lacourciere Y, et al. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. New Engl J Med. 1998;338:784–90.PubMedCrossRef
36.
Rohmeiss P, Birck R, Braun C, et al. Pharmacology of the endothelin A receptor antagonist: LU 135252. Cardiovasc Drug Rev. 1998;16:391–412.CrossRef
37.
Nakov R, Pfarr E, Eberle S, Investigators H. Darusentan: An effective endothelin A receptor antagonist for treatment of hypertension. Am J Hyper. 2002;15:583–9.CrossRef
38.
Black HR, Bakris GL, Weber MA, et al. Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study. J Clin Hyper. 2007;9:760–9.CrossRef
39.
Weber MA, Black H, Bakris G, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1423–31.PubMedCrossRef
40.
• Bakris GL, Lindholm LH, Black HR, et al. Divergent results using clinic and ambulatory blood pressures report of a darusentan-resistant hypertension trial. Hypertension. 2010;56:824–30. A large clincal trial where the decrease in BP with an ET A R selective antagonist was similar to placebo. This result terminated any future studies.PubMedCrossRef
41.
Webb DJ. DORADO: opportunity postponed lessons from studies of endothelin receptor antagonists in treatment-resistant hypertension. Hypertension. 2010;56:806–7.PubMedCrossRef
42.
Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet. 2001;357:1601–8.PubMedCrossRef
43.
Vaneckova I, Kramer HJ, Backer A, et al. Early endothelin-A receptor blockade decreases blood pressure and ameliorates end-organ damage in homozygous Ren-2 rats. Hypertension. 2005;46:969–74.PubMedCrossRef
44.
Koyama H, Nishzawa Y, Morii H, et al. Plasma endothelin levels in patients with uremia. Lancet. 1989;1:991–2.PubMedCrossRef
45.
Goddard J, Johnston NR, Cumming AD, Webb DJ. Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade. Am J Physiol. 2007;293:F1433–8.
46.
Orisio S, Benigni A, Bruzzi I, et al. Renal endothelin gene-expression is increased in remnant kidney and correlates with disease progression. Kidney Int. 1993;43:354–8.PubMedCrossRef
47.
Goddard J, Johnston NR, Hand MF, et al. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure - A comparison of selective and combined endothelin receptor blockade. Circulation. 2004;109:1186–93.PubMedCrossRef
48.
Dhaun N, MacIntyre IM, Melville V, et al. Blood pressure-independent reduction in proteinuria and arterial stiffness after acute endothelin-A receptor antagonism in chronic kidney disease. Hypertension. 2009;54:U113–U71.CrossRef
49.
Wu CD, Chan MF, Stavros F, et al. Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. J Med Chem. 1997;40:1690–7.PubMedCrossRef
50.
• Dhaun N, MacIntyre IM, Kerr D, et al. Selective endothelin-A receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. Hypertension. 2011;57:772. Reduction in blood pressure and cardiovascular risk factors with chronic ET A R selective antagonism in CKD.PubMedCrossRef
51.
Sarafidis PA, Bakris GL. Review: Insulin and endothelin: An interplay contributing to hypertension development? J Clin Endocrin Metabol. 2007;92:379–85.CrossRef
52.
Formoso G, Chen H, Kim JA, et al. Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium. Mol Endocrinol. 2006;20:1153–63.PubMedCrossRef
53.
van Harmelen V, Eriksson A, Astrom G, et al. Vascular peptide endothelin-1 links fat accumulation with alterations of visceral adipocyte lipolysis. Diabetes. 2008;57:378–86.PubMedCrossRef
54.
Wolpert HA, Steen SN, Istfan NW, Simonson DC. Insulin modulates circulating endothelin-1 levels in humans. Metabolism. 1993;42:1027–30.PubMedCrossRef
55.
Juan CC, Shen YW, Chien Y, et al. Insulin infusion induces endothelin-1-dependent hypertension in rats. Am J Physiol. 2004;287:E948–54.
56.
Cardillo C, Campia U, Bryant MB, Panza JA. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation. 2002;106:1783–7.PubMedCrossRef
57.
Shemyakin A, Bohm F, Wagner H, et al. Enhanced endothelium-dependent vasodilatation by dual endothelin receptor blockade in individuals with insulin resistance. J Cardiovasc Pharmacol. 2006;47:385–90.PubMed
58.
Amiri F, Virdis A, Neves MF, et al. Endothelium-restricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction. Circulation. 2004;110:2233–40.PubMedCrossRef
59.
Saleh MA, Boesen EI, Pollock JS, et al. Endothelin-1 increases glomerular permeability and inflammation independent of blood pressure in the rat. Hypertension. 2010;56:U942–427.CrossRef
60.
Barton M, Haudenschild CC, D'Uscio LV, et al. Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice. PNAS. 1998;95:14367–72.PubMedCrossRef
61.
Teerlink JR, Loffler BM, Hess P, et al. Role of endothelin in the maintenance of blood-pressure in conscious rats with chronic heart-failure—acute effects of the endothelin receptor antagonist RO-47-0203 (bosentan). Circulation. 1994;90:2510–8.PubMedCrossRef
62.
Humbert M, Segal ES, Kiely DG, et al. Results of european post-marketing surveillance of bosentan in pulmonary hypertension. Eur Resp J. 2007;30:338–44.CrossRef
63.
Ben-Yehuda O, Pizzuti D, Brown A, et al. Long-term hepatic safety of ambrisentan in patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2012;60:80–1.PubMedCrossRef
64.
Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Resp Crit Care Med. 2004;169:441–7.PubMedCrossRef
65.
Kohan D, Strait K, Stricklett P et al. Identification of the site of endothelin a receptor antagonist-induced fluid retention. Hypertension 2011,58:E155-E.
66.
Liu X, He L, Dinger B, et al. Effect of endothelin receptor antagonist bosentan on chronic hypoxia-induced inflammation and chemoafferent neuron adaptation in rat carotid body. High Alt Med Biol. 2012;13:209–16.PubMedCrossRef
67.
Clozel M, Breu V, Gray GA, et al. Pharmacological characterization of bosentan, a new potent orally-active nonpeptide endothelin receptor antagonist. J Pharmaocl Exp Ther. 1994;270:228–35.
Metadaten
Titel
Endothelin Antagonism and Its Role in the Treatment of Hypertension
verfasst von
Rebecca C. Moorhouse
David J. Webb
David C. Kluth
Neeraj Dhaun
Publikationsdatum
01.10.2013
Verlag
Springer US
Erschienen in
Current Hypertension Reports / Ausgabe 5/2013
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-013-0380-1

Weitere Artikel der Ausgabe 5/2013

Current Hypertension Reports 5/2013 Zur Ausgabe

Pediatric Hypertension (JT Flynn, Section Editor)

Determinants of Neonatal Blood Pressure

Hypertension Management and Antihypertensive Drugs (HM Siragy and B Waeber, Section Editors)

Novel Metabolic Drugs and Blood Pressure: Implications for the Treatment of Obese Hypertensive Patients?

Hypertension Management and Antihypertensive Drugs (HM Siragy and B Waeber, Section Editors)

Effectiveness and Safety of Phosphodiesterase 5 Inhibitors in Patients with Cardiovascular Disease and Hypertension

Pediatric Hypertension (JT Flynn, Section Editor)

Primary Hypertension in Childhood

Pediatric Hypertension (JT Flynn, Section Editor)

Sodium Intake and Blood Pressure in Children

Pediatric Hypertension (JT Flynn, Section Editor)

Left Ventricular Hypertrophy in Hypertensive Children and Adolescents: Predictors and Prevalence

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

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

Newsletter bestellen
Bildnachweise