Angiographic demonstration of hyperconstriction induced by serotonin and aggregating platelets in porcine coronary arteries with regenerated endothelium

Abstract

In isolated porcine coronary arteries, the endothelium inhibits the contractions induced by serotonin and aggregating platelets. This effect is reduced by regeneration after balloon denudation. The present study was designed to examine whether those in vitro observations could be reproduced in vivo. Sixteen male Yorkshire pigs underwent balloon removal of the endothelium from either the left anterior descending (n = 9) or left circumflex (n = 7) coronary artery. An angiographic study was performed before and 4 weeks after endothelial denudation; in the latter condition the presence of a full endothelial lining was confirmed histologically. Before endothelial denudation, intracoronary injection of serotonin (10 micrograms/kg) caused only mild constriction in both arteries. However, 4 weeks after the denudation, intracoronary serotonin repeatedly caused marked hyperconstriction in the previously denuded artery compared with the control coronary artery. Intracoronary injection of aggregating platelets stimulated by collagen caused constriction in the previously denuded artery but not in the control artery. The hyperconstriction induced by serotonin and aggregating platelets was inhibited by intravenous injection of ketanserin (a 5-HT2-serotonergic blocker). These data indicate that 1) the normal endothelium blunts the coronary vasoconstriction induced by serotonin and aggregating platelets in vivo, and 2) the inhibitory effect of the endothelium is reduced after regeneration, allowing coronary hyperconstriction or vasospasm, or both.