Combination of low-dose valsartan and enalapril improves endothelial dysfunction and coronary reserve in Nomega-nitro-L-arginine methyl ester-treated spontaneously hypertensive rats.

Combination of nonhypotensive doses of valsartan and enalapril markedly improved survival (+87%) compared with untreated animals (37%) in spontaneously hypertensive rats (SHRs) with endothelial dysfunction. However, the combination had no effect on kidney function, and proteinuria persisted over the 12 weeks of the study. It was hypothesized that the greater survival was due to improvement in endothelial function or coronary vasculature despite blockade of nitric oxide synthase and high blood pressure.

Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction.

There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy.

Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.

Objective: Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was studied in rats chronically treated with bosentan after myocardial infarction.

Methods: Rats were subjected to coronary artery ligation and were treated for 8 weeks with placebo or bosentan, a dual ET(A) and ET(B) receptor antagonist, (approximately 100 mg/kg/day) as food admix. Sham-operated rats served as normal controls.

Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction.

Objectives: We investigated the effects of short-term tezosentan treatment on cardiac function, pulmonary edema and long-term evolution of heart failure (HF) in a rat model of myocardial infarction (MI).

Background: Endothelin (ET) may play a major role in the progression from MI to HF. Tezosentan is a new dual ET(A)/ET(B) receptor antagonist.

Additional effects of endothelin receptor blockade and angiotensin converting enzyme inhibition in rats with chronic heart failure.

Aim: To evaluate the acute effects of tezosentan, a new dual parenteral endothelin receptor antagonist, on hemodynamics in a rat model of chronic heart failure (CHF), and further investigated if the combination of tezosentan with the angiotensin converting enzyme (ACE) inhibitor, enalapril, had additive hemodynamic effect.

Methods: Hemodynamics was measured in rats with CHF, induced by ligation of the left coronary artery.

Results: At 3 to 5 weeks after myocardial infarction, rats developed CHF.