Endothelin in heart failure.

Congestive heart failure is a complex disease that results from pumping failure of the cardiac muscle and adaptational processes of the cardiovascular system to correct for the reduced blood supply to the organism. It is associated with increased vasoconstriction and impaired vasodilation in response to physical activity. The elevated vasoconstrictor tone is caused by the activation of compensatory mechanisms including the sympathetic nervous system and stimulation of the release of neurohormones like angiotensin II, catecholamines, and vasopressin. Furthermore, the vascular endothelium is importantly involved in the regulation of vascular tone as it releases a variety of vasoactive substances that act locally and systemically. In congestive heart failure, there is a marked imbalance between the diminished release or the increased inactivation of vasodilators on the one hand, ie, nitric oxide, and the elevated production, release, or reduced inactivation of vasoconstrictors such as endothelin-1 on the other hand. In addition to its very potent vasoconstrictor effects, endothelin-1 possesses antinatriuretic and mitogenic properties that are a common feature of substances that are involved in development of the deleterious consequences that render congestive heart failure a lethal disease. The spectrum of action of the endothelin system and the advent of specific antagonists for its receptors have made this system a very interesting target for clinical research and possibly for future therapeutic approaches.