The purpose of this study was to determine the role of endothelin in mediating the renal hemodynamic and arterial pressure changes observed during chronic ANG II-induced hypertension. ANG II (50 ng x kg(-1) x min(-1)) was chronically infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley rats with and without endothelin type A (ET(A))-receptor antagonist ABT-627 (5 mg...

BACKGROUND The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of the microcirculatory dysfunction seen in sepsis. The mixed endothelin receptor antagonist tezosentan and the selective endothelin A-receptor antagonist TBC3711 were used to investigate the importance of the different endothelin receptors in modulating splanchnic regional blood flow and microvascular bl...

RES-701-2, -3 and -4, novel cyclic peptide endothelin antagonists, were isolated from the culture broths of Streptomyces sp. RE-701 and RE-896, RES-701s selectively inhibited the ET-1 binding to endothelin type B receptor (ETB receptor) with IC50 values ranging from 5 to 20 nM. Taxonomy of the producing strains, fermentation, isolation and biochemical properties of RES-701s are described.

BACKGROUND Endothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ETA receptor, which preferentially binds ET-1, and the ETB receptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein ...

BACKGROUND Endothelin-1 is a potent vasoconstrictor and smooth-muscle mitogen. In a preliminary study, the orally administered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension. The present trial investigated the effect of bosentan on exercise capacity in a larger number of patients and compa...

Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hyper...

BACKGROUND To test the hypothesis that endothelin-1 contributes to cardiac fibrosis, cardiac collagen deposition was studied in deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, in which the endothelin system is activated. The effects of the ET(A)-selective endothelin receptor antagonist A-127722 were evaluated. METHODS AND RESULTS A-127722 (30 mg/kg per day) was administered fo...

The heart failure syndrome is associated with a reduced vasodilatory capacity in cutaneous microvessels. The aim of this study was to investigate the hypothesis that an altered activity of the endothelin system contributes to this reduction. The skin blood flow was recorded by laser Doppler flowmetry in patients with congestive heart failure and in age- and gender-matched controls without clini...

At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. The current CHF pharmacotherapy is complex, involving factors affecting the renin-angiotensin-aldosterone system (RAAS), beta-blockers, diuretics and vasodilatators. There are also significant efforts to introduce in CHF pharmacology novel therapeutic strategies, based o...