Role of Endogenous Endothelin in Chronic Heart Failure

• DOI: 10.1161/01.cir.96.6.1976
• Publication Date: 2012-06-12T00:41:02Z
• Authors: Paul Mulder; Vincent Richard; Geneviève Derumeaux; Manuela Hogie; Jean Paul Henry; Françoise Lallemand; Patricia Compagnon; Bertrand Macé; Etienne Comoy; Brice Letac; Christian Thuillez
• Keywords: Afterload; Preload; Endothelin receptor antagonist; Ventricular pressure

Plasma levels of the vasoconstrictor peptide endothelin (ET) are increased in chronic heart failure (CHF), and ET a major predictor mortality this disease. Thus, may play deleterious role CHF. The purpose study was to assess effects treatment with receptor antagonist bosentan rat model CHF.Rats were subjected coronary artery ligation treated for 2 or 9 months placebo (30 100 mg x kg(-1) d(-1)). Bosentan markedly survival (after months: untreated, 47%; bosentan, 65%; P<.01). Throughout 9-month period, significantly reduced arterial pressure rate. After treatment, central venous left ventricular (LV) end-diastolic as well plasma catecholamines, urinary cGMP, LV collagen density. also dilatation (evidenced at by shift pressure/volume relationship ex vivo). Echocardiographic studies performed after showed that hypertrophy contractility noninfarcted wall. lower dose kg(-1)), which had no hemodynamic structural effects, effect on survival.Long-term an increases This increase is associated decreases both preload afterload cardiac output decreased hypertrophy, dilatation, fibrosis. antagonists such might be beneficial human CHF long-term