Inhibition of hypoxic coronary vasoconstriction by pinacidil.
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 hypoxia-induced 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 gas mixture from 95% O2/5% CO2 to 95% N2/5% CO2 in preparations partially contracted with KCl. 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.
O'Rourke
S T
ST
Department of Pharmaceutical Science, College of Pharmacy, North Dakotae University, Fargo 58105, USA.
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005069:Evaluation Studies as Topic; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D020110:Pinacidil; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil; D010100:Oxygen