ENDOTHELIN-1 IS NOT INVOLVED IN SEROTONIN-INDUCED CORONARY SPASM IN ASWINE MODEL

Objectives: The role of endothelin-l (ET-1) in the pathogenesis of cor onary 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 descend ing coronary artery was denuded and irradiated with X-ray. Three month s after endothelial denudation, coronary vasomotion was assessed in vi vo by quantitative arteriography. Results: Intracoronary serotonin at 10 mu g/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. Int racoronary administration of ET-1 at 25 ng/kg caused mild vasoconstric tion 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 an tagonist (BQ123 0.1 mg/kg) significantly attenuated coronary vasoconst riction and ST segment elevation evoked with ET-1, but did not alter s erotonin-induced vasoconstriction either at the denuded or control sit e. 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.