Endothelin in Congestive Heart Failure: Pathophysiology and Therapeutic Implications

Abstract

Activation of both tissue and circulating endothelin-1 (ET) has emerged as an additional neurohumoral hallmark of congestive heart failure (CHF). The mechanism of activation of ET in CHF probably is multifactorial and includes stimulation by factors such as Angiotensin II and tissue hypoxia. The functional significance of ET activation in CHF is currently being elucidated by the use of potent ET receptor antagonists. Such studies support the concept that ET in CHF contributes to vasoconstriction, alterations in other neurohumoral systems and ventricular hypertrophy. The increase of plasma ET in CHF also has prognostic and diagnostic significance thus supporting its role as a serum marker in the management of CHE Moreover, the high mortality associated with CHF may be decreased by interrupting the ET system thus supporting the inhibition of ET as a treatment strategy. Thus, ET emerges as both a marker and mediator of CHF as well as a key target in the therapeutics for this important cardiovascular disease.