ROLE OF ENDOGENOUS ENDOTHELIN IN NORMAL HEMODYNAMIC STATUS OF ANESTHETIZED DOGS

Endothelin (ET) is a potent vasoconstrictor that may be involved in a number of cardiovascular disorders, although its role in normal hemody namics remains unclear. Twenty-two anesthetized open-chest dogs were i nstrumented for measurement of systemic and pulmonary hemodynamics, ca rdiac output, coronary blood flow, and cardiac contractility. Big ET i nduced peripheral and coronary vasoconstriction, which occurred before significant elevations in plasma ET and which was nearly completely b locked by bosentan, a new nonpeptidic mixed (ET(A) and ET(B)) ET recep tor antagonist. Bosentan also prevented the peripheral dilatation caus ed by the specific ET(B) receptor agonist, sarafotoxin S6c, but did no t prevent the peripheral vasoconstriction induced by angiotensin II. B osentan alone had no significant hemodynamic effect in the normal anes thetized dog, although it did induce a reactive increase in the plasma level of ET-1 and ET-3. This study demonstrates that, despite blockin g both ET(A) and ET(B) receptors, bosentan alone had no hemodynamic ef fect, suggesting that ET does not play a major role in the normal hemo dynamic status of anesthetized dogs.