Differential effects of the antianginal drug nicorandil on canine arteries and veins.
Nicorandil, a potent coronary vasorelaxant used in the treatment of angina, has differential effects on arteries and veins in vivo. To explain this phenomenon, experiments were designed to characterize the relaxant and inhibitory actions of this compound on canine isolated arteries and veins. Paired rings of canine coronary, femoral, and saphenous arteries and saphenous veins were suspended at optimal length for isometric tension recording in organ chambers containing physiologic salt solution at 37 degrees C and gassed with 95% O2-5% CO2. In certain experiments, one ring of each pair was denuded of the endothelium. Removal of the endothelium did not affect nicorandil-induced relaxations of contracted blood vessels. Nicorandil exerted a differential relaxant effect on arteries and veins contracted with KCl (order of potency: saphenous vein greater than coronary artery greater than femoral artery). No difference in sensitivity to nicorandil was observed in arteries and veins contracted with prostaglandin F2 alpha. Contractions of saphenous arteries and veins to norepinephrine (NE) were equally sensitive to the inhibitory action of nicorandil. However, contractions of saphenous veins induced by sympathetic nerve stimulation were more sensitive to nicorandil than were contractions of saphenous arteries. Furthermore, nicorandil did not affect contractions to phenylephrine in saphenous veins, although contractions to B-HT 920 were virtually abolished by the compound. Saphenous veins contracted with St 587 were more sensitive to the relaxant action of nicorandil than when contracted with phenylephrine. These results suggest that nicorandil inhibits preferentially contractions of canine arteries and veins mediated by alpha 2- rather than alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Morrison
K J
KJ
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Flavahan
N A
NA
Vanhoutte
P M
PM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D014665:Vasodilator Agents; D010656:Phenylephrine; D009536:Niacinamide; D020108:Nicorandil; C024763:talipexole; D015237:Dinoprost; D009638:Norepinephrine