ROLE OF ENDOTHELIN IN HEART FUNCTION IN HEALTH AND DISEASE

A comprehensive review of the literature has revealed that endothelins belong to a family of vasoactive peptides which are formed and releas ed from the endothelium. By producing constriction of the coronary art eries and peripheral blood vessels, endothelins are known both to redu ce coronary bloodflow and increase blood pressure and thus can be seen to affect heart function adversely. On the other hand, endothelins ar e capable of producing positive inotropic and chronotropic effects by directly affecting both the myocardium and nodal tissues. Prolonged ac tions of high concentrations of endothelins can be seen to induce rela tive hypoxia in the myocardium which will eventually result in heart d ysfunction. The mechanisms of actions of endothelin on smooth muscle c ells and cardiomyocytes include interaction with endothelin receptors on the cell surface, activation of phospholipase C through G-proteins, and increase in the intracellular concentration of Ca2+ through the i ncrease in phosphoinositol turnover. Endothelins were found to exert n o effects on sarcolemmal Na+,K+-ATPase, Na+-Ca2+ exchange and Ca2+ pum p systems nor on the sarcoplasmic reticular Ca2+ pump system and myofi brillar ATPase activities in the rat heart. Marked elevation in the le vels of plasma endothelins and down-regulation of endothelin receptors in ischemia-reperfusion injury, hypertension and chronic diabetes ind icate a significant role of endothelins in the genesis of heart dysfun ction under different pathological conditions.