Endothelin-1 is not involved in serotonin-induced coronary spasm in a swine model

Objectives: The role of endothelin-1 (ET-1) in the pathogenesis of coronary artery spasm is not well understood. We aimed to determine if ET-1 is involved in serotonin-induced coronary spasm in the swine model. Methods: In 10 miniature pigs, a segment of the left anterior descending coronary artery was denuded and irradiated with X-ray. Three months after endothelial denudation, coronary vasomotion was assessed in vivo by quantitative arteriography. Results: Intracoronary serotonin at 10 μg/kg provoked coronary spasm (augmented narrowing of the luminal diameter) at the denuded site (diameter reduction 93 ± 4%) but not at the non-denuded control site (19 ± 4%, P < 0.01) associated with ST segment elevation in the region perfused by the denuded artery. Intracoronary administration of ET-1 at 25 ng/kg caused mild vasoconstriction of the denuded (26 ± 4) and non-denuded site (16 ± 3%, n.s.), but provoked ST segment elevation in the regions perfused by both the denuded and non-denuded arteries. The treatment with an endothelin antagonist (BQ123 0.1 mg/kg) significantly attenuated coronary vasoconstriction and ST segment elevation evoked with ET-1, but did not alter serotonin-induced vasoconstriction either at the denuded or control site. Conclusions: The results of this study suggest that endogenous ET-1 may not be involved in the pathogenesis of serotonin-induced coronary spasm in our swine model.