Effect of endothelin on the function of the isolated perfused working rat heart.

1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined. 2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected. 3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed. 4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 mumol/l). 5. In the presence of either nicardipine (0.5 mumol/l) or verapamil (0.2 mumol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers. 6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.