A NOVEL MODEL OF CONDUIT CORONARY CONSTRICTION REVEALS LOCAL ACTIONS OF ENDOTHELIN-1 AND PROSTAGLANDIN-F2-ALPHA

We evaluated the effects of endothelin-1 (ET-1) and prostaglandin F-2 alpha (PGF(2 alpha)) selectively on conduit coronary artery diameter u sing a novel approach in which the local concentration of vasoactive a gent was controlled and maintained in vivo. ET-1 and PGF(2 alpha) were applied topically (100 mu l every 3 min) to the external surface of t he left circumflex coronary artery (LCx) in anesthetized dogs or to th e bathing medium of isolated canine LCx rings in parallel in vitro exp eriments. The dose-dependent constrictions obtained in vivo and in vit ro were similar with each agent. Single, approximately maximally effec tive concentrations of PGF(2 alpha) evoked an initial rapid contractio n followed by a slow and sustained larger contraction in both preparat ions. In contrast, single concentrations of ET-1 elicited a rapid cons triction that partially recovered (50-80%) in the ensuing 1.5-2 h desp ite continuous exposure to ET-1. After the ET-1 constriction reversed, PGF(2 alpha) could still elicit a contraction, indicating a homologou s endothelin receptor desensitization. Both agents maximally decreased conduit artery cross-sectional area in vivo by similar to 40% without significantly changing LCx resistance. Thus this in situ technique re vealed effects of ET-1 and PGF(2 alpha) on a localized segment of coro nary artery that were not discernible with either intravenous or intra coronary administration.