title: Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries.
abstract: The relaxant mechanisms of action of cromakalim, pinacidil and nicorandil, potassium channel openers, on large epicardial coronary arteries were investigated in isolated canine left circumflex arteries contracted by 10(-7) mol/l U46619, a thromboxane A2 analogue, or addition of 25 mmol/l KCl in comparison with nitroglycerin. Cromakalim (3 x 10(-8)-3 x 10(-5) mol/l), pinacidil (10(-6)-10(-4) mol/l), nicorandil (3 x 10(-6)-10(-3) mol/l) and nitroglycerin (3 x 10(-8)-10(-5) mol/l) all produced a concentration-dependent relaxation in both U46619- or KCl-contracted arteries. At their maximum effects pinacidil, nicorandil and nitroglycerin produced full relaxation in arteries contracted by either means. In contrast, cromakalim produced about a 73% relaxation in KCl-contracted arteries, although it caused full relaxation in U46619-contracted ones. In the presence of glibenclamide the concentration-relaxation curves for cromakalim in U46619- or KCl-contracted arteries underwent rightward parallel shifts. Schild regression had a slope of 1.00 and yielded a pA2 of 7.47 for glibenclamide in U46619-contracted arteries, and corresponding values obtained in KCl-contracted arteries were 0.86 (not significantly different from unity) and 7.28. The concentration-relaxation curves for pinacidil in U46619-contracted arteries also underwent rightward parallel shifts in the presence of glibenclamide, however, Schild regression had a slope of 0.60. The concentration-relaxation curves for pinacidil in KCl-contracted arteries underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide. The concentration-relaxation curves for nicorandil and nitroglycerin in U46619- or KCl-contracted arteries were not affected by glibenclamide in concentrations which antagonized cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Taira
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D020110:Pinacidil; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D006146:Guanidines; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020110:Pinacidil; D005996:Nitroglycerin; D011188:Potassium; D005905:Glyburide; D008751:Methylene Blue