Endothelin‐1 receptor antagonism does not influence myocardial function in hypertensive dogs

Massart, Pascale; Hodeige, D; Mechelen, Henri Van; Heyndrickx, Guy R.; Donckier, Julian

doi:10.1046/j.1365-2362.1998.00374.x

Cited by 2 publications

(1 citation statement)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…133 Despite the known positive inotropic effect of ET-1, bosentan reduces arterial pressure in dogs with perinephritic hypertension and in DOCA-salt hypertensive rats, by decreasing total peripheral resistance without affecting myocardial contractility. 100,134 In humans with essential hypertension, the ET A -and ET B -receptor antagonist,TAK-044, caused greater forearm vasodilatation compared with normotensive controls, perhaps because of decreased ET B -mediated tonic NO release from endothelial cells in essential hypertension. 135 Combined blockade of ET A -and ET B -receptors, by BQ-123 and BQ-788, results in greater forearm vasodilatation than selective ET A -receptor blockade by BQ-123 in patients with essential hypertension.…”

Section: Anti-endothelin Agents In Essential Hypertensionmentioning

confidence: 99%

Role of endothelin in cardiovascular disease

Agapitov

Haynes

2002

J Renin Angiotensin Aldosterone Syst

154

119

View full text Add to dashboard Cite

Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system.

show abstract

Section: Anti-endothelin Agents In Essential Hypertensionmentioning

confidence: 99%

Role of endothelin in cardiovascular disease

Agapitov

Haynes

2002

J Renin Angiotensin Aldosterone Syst

154

119

View full text Add to dashboard Cite

show abstract

Untitled

Donckier

2001

Heart Failure Reviews

View full text Add to dashboard Cite

Since its discovery in 1988, there has been increasing evidence that endothelin-1 (ET-1) plays an important role in the pathophysiology of hypertension and its related end-organ damages. First studies, using ET-1 administration in animals or in humans suspected this role by demonstrating the hypertensive properties of ET-1. The latter, due to stimulation of ET(A) receptors inducing sustained vasoconstriction have been reported to follow transient vasodilation linked with activation of an endothelial ET(B) receptor releasing nitric oxide (NO). In certain instances, ET(B) smooth-muscle receptors might also induce contraction. Cloning of these receptors helped to develop ET-1 receptor antagonists. As soon as one of them became available, bosentan, a dual (ET(A) and ET(B)) ET-1 receptor antagonist, we tested its effects in the canine model of perinephritic hypertension. Bosentan was found to exert striking hypotensive effects, due to peripheral vasodilation but without affecting cardiac function. In further experiments, we observed that effects of bosentan were additional to those of ACE inhibitors or angiotensin II antagonists. This opened new therapeutic perspectives and also suggested a proper role of ET-1 in hypertension, independent of the renin-angiotensin system. To explain this role, we demonstrated a real imbalance characterized by an impairment of the NO system in favor of the ET-1 pathway. Recent studies suggest that such an imbalance may also occur in human hypertension. Furthermore, the contribution of ET-1 to human hypertension appears more convincing since bosentan was shown to decrease blood pressure in hypertensive subjects. Finally, ET-1 receptor antagonists might be of therapeutic interest to prevent hypertension induced end-organ damages. Whether or not these compounds are able to prevent or to reverse target organ injuries in man remains to be investigated.

show abstract

Endothelin‐1 receptor antagonism does not influence myocardial function in hypertensive dogs

Abstract: Without influencing heart function, bosentan is an efficient and safe therapy that opens up new therapeutic perspectives in human essential hypertension.

Cited by 2 publications

References 41 publications

Role of endothelin in cardiovascular disease

Role of endothelin in cardiovascular disease

Untitled

Contact Info

Product

Resources

About