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  • Title: Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries.
    Author: Satoh K, Yamada H, Taira N.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1991 Jan; 343(1):76-82. PubMed ID: 1827660.
    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)
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