Inhibition of hypoxic coronary vasoconstriction by pinacidil

Abstract

Acute hypoxia causes constriction of isolated coronary arteries from several species. The present study was designed to test whether pinacidil, a potassium channel opener, inhibits hypoxiainduced contraction of porcine isolated coronary arteries. Coronary arterial rings were suspended in organ baths for isometric tension recording. Hypoxic contractions were evoked by rapidly changing the gas mixture from 95% O 2/5% CO 2 to 95% N 2/5% CO 2 in preparations partially contracted with KC1. Pretreatment with pinacidil (10 −6 to 10 −4 M) caused concentration-dependent inhibition of the contractile response to hypoxia. The inhibitory effect of pinacidil was attenuated by the k atp channel blocker, glibenclamide (10 −6 M). In rings contracted with acetylcholine, glibenclamide caused a rightward shift in the concentration-response curve to pinacidil while having no effect on the vasorelaxant responses to sodium nitroprusside and diltiazem, thus confirming the specificity of glibenclamide for potassium channel opener-mediated responses. Taken together, the data indicate that pinacidil prevents hypoxia-induced contraction of porcine coronary arteries, and that the effect of pinacidil may be mediated by the opening of glibenclamide-sensitive potassium channels.