Endothelin mediates the altered renal hemodynamics associated with experimental congestive heart failure

Congestive heart failure (CHF) is commonly associated with renal dysfunctio n. The goal of the current study was to evaluate the role of endothelin in the renal dysfunction of experimental CHF by using tezosentan, a potent dua l endothelin receptor antagonist. Rats were subjected to coronary artery li gation. Cardiac and renal hemodynamics were assessed after 3-5 weeks, when CHF had developed. Compared with control rats, CHF rats had significantly h igher left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and reduced dP/dt(max). CHF rats had severe renal vasoconstrictio n, as assessed by increased renal vascular resistance (RVR, p < 0.001), dec reased renal plasma flow (RPF, p < 0.001), and glomerular filtration rate ( GFR, p < 0.001). Filtration fraction rose (p < 0.001). Urine flow rate and sodium excretion were markedly lower. Acute administration of tezosentan in duced a marked decrease in LVEDP without change of dP/dt(max) and heart rat e. Tezosentan decreased RVR (-43%, p < 0.001) and increased RPF and GFR. Fi ltration fraction decreased slightly, Tezosentan also increased urine flow rate and sodium excretion. These findings demonstrate that endothelin at le ast partly mediates the altered renal hemodynamics associated with experime ntal CHF. Dual endothelin receptor blockade could be useful for the improve ment of both cardiac and renal function in CHF.