ENDOTHELIN-1 INCREASES ARTERIAL SENSITIVITY TO 5-HYDROXYTRYPTAMINE

Rings of rabbit abdominal aorta were pretreated with endothelin-1 (ET-1) or vehicle and then isometric contractions to cumulative additions of 5-hydroxytryptamine (5-HT) were recorded. ET-1 at concentrations of 0.4, 1 and 2 nM produced contractions of 7, 15 and 35% of maximal potassium chloride-induced contractions, respectively. Pretreatment of aortic rings with these concentrations of ET-1 increased (P < 0.01) arterial sensitivity (EC50) to 5-HT 1.9-, 2.4- and 3.5-fold, respectively, without affecting peak 5-HT-induced force. Acetylcholine-induced, endothelium-dependent aortic relaxations were not affected by pretreatment with ET-1. Removal of the endothelium potentiated aortic responses to ET-1 and to 5-HT-induced contractions of ET-1-pretreated but not untreated aortic rings. These results suggest that ET-1 could promote arterial vasospasm by sensitizing the artery to 5-HT released from platelets. © 1990.