PHYSIOLOGICAL SIGNIFICANCE OF ENDOTHELIN - ITS ROLE IN CONGESTIVE-HEART-FAILURE

Endothelin (ET) is a endothelium-derived peptide with potent vasoconst rictor and growth-promoting actions. Although its physiological role r emains unclear, recent studies report increased ET in various pathophy siological states, including congestive heart failure (CHF). The mecha nisms contributing to increased ET in CHF probably include hemodynamic factors like increased atrial and venous pressures and reduced perfus ion pressure and shear stress. Recent investigations also suggest that the kidney, lung, heart, and peripheral vasculature are sites of ET m essenger RNA expression that may contribute to the elevation of ET in pathophysiological states. Recent studies have demonstrated that ET in fusion to mimic pathophysiological levels has important biological act ions, suggesting that ET may play an important role as a circulating h ormone to maintain adequate perfusion during CHF. However, recent repo rts demonstrate that endogenous vasodilators like atrial natriuretic f actor and endothelium-derived relaxing factor may attenuate ET actions in vivo. In conclusion, ET is a potent vasoconstricting and mitogenic peptide of endothelial origin that may participate in the adaptations to acute reductions in perfusion pressure in CHF. As this syndrome pr ogresses, ET may contribute to the systemic vasoconstriction and cardi ac vascular remodeling that characterize severe CHF. It is likely that therapeutic regimens that block or prevent the activation of ET or an tagonize its actions may have a beneficial role in the treatment of he art failure.