Positive Inotropic and Vasoconstrictive Effects of Endothelin-1 in in vivo and in vitro Experiments

Abstract

Cardiac and vascular effects of endothelin-1 (ET-1) were studied in hemodynamic models in vivo and in isolated artery and heart tissues. The hemodynamic changes induced by ET-1 (30-300 pmol/kg i.v.) in dogs were increases in blood pressure, cardiac output, and ventricular contractility. Ring preparations of canine coronary artery and rabbit thoracic aorta showed vasoconstrictive responses to ET-1 (10(-10) M and over) with an EC50 of 3-10 x 10(-9) M. Nifedipine 10(-5) M did not reverse these effects completely. ET-1 had positive inotropic effects from 10(-10) M in rabbit papillary muscles. It lengthened the action potential duration by 16% and increased the developed tension by 180% (10(-8) M). In contrast, Bay K 8644 (10(-7) M) produced similar lengthening (17%) in the duration with only a 37% increase in the tension. This suggests a difference in the mechanisms of the positive inotropic effects between these two agents. We conclude that ET-1 has positive inotropic and vasoconstrictive effects, and that these ET-1-induced contractions in ventricular muscles and arteries cannot be explained thoroughly by the increase in currents through voltage-dependent calcium channels.