A novel model of conduit coronary constriction reveals local actions of endothelin-1 and prostaglandin F2alpha

Abstract

We evaluated the effects of endothelin-1 (ET-1) and prostaglandin F2alpha (PGF2alpha) selectively on conduit coronary artery diameter using a novel approach in which the local concentration of vasoactive agent was controlled and maintained in vivo. ET-1 and PGF2alpha were applied topically (100 microl every 3 min) to the external surface of the left circumflex coronary artery (LCx) in anesthetized dogs or to the bathing medium of isolated canine LCx rings in parallel in vitro experiments. The dose-dependent constrictions obtained in vivo and in vitro were similar with each agent. Single, approximately maximally effective concentrations of PGF2alpha evoked an initial rapid contraction followed by a slow and sustained larger contraction in both preparations. In contrast, single concentrations of ET-1 elicited a rapid constriction that partially recovered (50-80%) in the ensuing 1.5-2 h despite continuous exposure to ET-1. After the ET-1 constriction reversed, PGF2alpha could still elicit a contraction, indicating a homologous endothelin receptor desensitization. Both agents maximally decreased conduit artery cross-sectional area in vivo by approximately 40% without significantly changing LCx resistance. Thus this in situ technique revealed effects of ET-1 and PGF2alpha on a localized segment of coronary artery that were not discernible with either intravenous or intracoronary administration.