A novel model of conduit coronary constriction reveals local actions of endothelin-1 and prostaglandin F2alpha.
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.
Rigel
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DF
Research Department, Pharmaceuticals Division, Ciba-Geigy Corporation, Summit, New Jersey 07901, USA.
Shetty
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SS
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction; D016277:Ventricular Function, Left / Q000187:drug effects
D019332:Endothelin-1; D015237:Dinoprost