Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs
Summary
Nicorandil possesses hybrid properties as a nitrate and a potassium (K) channel opener. We have previously reported that large coronary arteries responded to nicorandil at low plasma concentrations, while dilatation of small coronary arteries only occurred at higher plasma concentrations (above 200 ng/ml) in chronically instrumented dogs. In this study we examined the effects of intravenous nicroandil on epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) in the absence and presence of glibenclamide, a K+ channel blocker, as well as the effects of nitroglycerin and cromakalim as reference drugs. The increase in CBF induced by nicorandil and cromakalim was significantly suppressed by glibenclamide. However, the increase in CoD induced by nicorandil and nitroglycerin was not suppressed by glibenclamide. These findings suggest that nicorandil-induced dilatation of the large coronary arteries was related to its nitrate action, while nicorandil-induced dilatation of the small coronary arteries was closely related to its effect as a K+ channel opener. In addition, the former response to nicorandil occurred at low concentrations, while the latter occurred at higher concentrations.
Key Words
nicorandil glibenclamide coronary artery diameter coronary blood flow K+ channelPreview
Unable to display preview. Download preview PDF.
References
- 1.Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators.Am J Cardiol 1989;63:18J-24JPubMedGoogle Scholar
- 2.Yanagisawa T, Hashimoto H, Taira N. The negative inotropic effect of nicorandil is independent of cyclic GMP changes: A comparison with pinacidil and cromakalim in canine atrial muscle.Br J Pharmacol 1988;95:393–398.PubMedGoogle Scholar
- 3.Taira N. Similarity and dissimilarity in the mode and mechanism of action between nicorandil and classical nitrates: An overview.J Cardiovasc Pharmacol 1987;10(Suppl 8):S1-S9.Google Scholar
- 4.Satoh K, Yamada H, Taira N. Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries.Naunyn Schmiedebergs Arch Pharmacol 1991;343:76–82.PubMedGoogle Scholar
- 5.Yamada H, Yoneyama F, Satoh K, Taira N. Specific but differential antagonism by glibenclamide of the vasode-pressor effects of cromakalim and nicorandil in spinally-anaesthetized dogs.Br J Pharmacol 1990;100:413–416.PubMedGoogle Scholar
- 6.Meisheri KD, Cipkus-Dubray LA, Hosner JM, Khan SA. Nicorandil-induced vasorelaxation: Functional evidence for K+ channel-dependent and cyclic GMP-dependent components in a single vascular preparation.J Cardiovasc Pharmacol 1991;17:903–912.PubMedGoogle Scholar
- 7.Kukovetz WR, Holzmann S, Braida C, Pöch G. Dual mechanism of the relaxing effect of nicorandil by stimulation of cyclic GMP formation and by hyperpolalization.J Cardiovasc Pharmacol 1991;17:627–633.PubMedGoogle Scholar
- 8.Yoneyama F, Satoh K, Taira N. Nicorandil increases coronary blood flow predominantly by K-channel opening mechanism.Cardiovasc Drugs Ther 1990;4:1119–1126.PubMedGoogle Scholar
- 9.Imagawa J, Akima M, Nabata H, Taira N. Spasmolytic action of nicorandil in canine conductive coronary arteries in vivo is not modified by glibenclamide.J Cardiovasc Pharmacol 1992;19:108–114.PubMedGoogle Scholar
- 10.Ogawa N, Fukata Y, Kaneta S, Jinno Y, Fukushima H, Nishikori K. Comparison of KRN2391 with nicorandil and nifedipine on canine coronary blood flow: antagonism by glibenclamide.J Cardiovasc Pharmacol 1992;20:11–17.PubMedGoogle Scholar
- 11.Goodman CC, Castellana FS. A digital sonomicrometer for two-point length and velosity measurements.Am J Physiol 1982;243:H634-H639.PubMedGoogle Scholar
- 12.Schmid-Antomarchi H, De Weille J, Fosset M, Lazdunsky M. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulinsecreting cells.J Biol Chem 1987;262:15840–15844.PubMedGoogle Scholar
- 13.Weir SW, Weston AH. The effects of BRL 34915 and nico-randil on electrical and mechanical activity and on86Rb efflux in rat blood vessels.Br J Pharmacol 1986;88:121–128.PubMedGoogle Scholar
- 14.Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle.Science 1989;245:177–180.PubMedGoogle Scholar
- 15.Fujii K, Foster CD, Brading AF, Parekh AB. Potassium channel blockers and the effects of cromakalim on the smooth muscle of the guinea-pig bladder.Br J Pharmacol 1990;99:779–785.PubMedGoogle Scholar
- 16.Piper I, Minshall E, Downing SJ, Hollingsworth M, Sadraei H. Effects of several potassium channel openers and gliben-clamide on the uterus of the rat.Br J Pharmacol 1990;101:901–907.PubMedGoogle Scholar
- 17.Wickenden AD, Grimwood S, Grant TL, Todd MH. Comparison of the effects of the K+-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.Br J Pharmacol 1991;103:1148–1152.PubMedGoogle Scholar
- 18.Weik R, Neumcke B. Effects of potassium channel openers on single potassium channels in mouse skeletal muscle.Naunyn Schmiedebergs Arch Pharmacol 1990;342:258–263.PubMedGoogle Scholar
- 19.Nelson MT, Patlak JB, Worley JF, Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone.Am J Physiol 1990;259:C3-C18.PubMedGoogle Scholar
- 20.Chu A, Murray JJ, Lin CC, Russel M, Hagen PO, Cobb FR. Preferential proximal coronary dilation by activators of guanylate cyclase in awake dogs.Am J Physiol 1990;259:H340-H345.PubMedGoogle Scholar
- 21.Hashimoto K, Kinoshita M, Ohbayashi Y. Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs.Cardiovasc Drugs Ther 1991;5:131–138.PubMedGoogle Scholar
- 22.Iinuma H, Kuboki M, Kato K. Effect of nicorandil on variant angina pectoris.Saishin Igaku 1983;37:2422–2426 (in Japanese).Google Scholar
- 23.Uchida Y, Sugimoto T. The effects of nicorandil on phasic contractions of isolated canine coronary artery.J Cardiovasc Pharmacol 1987;10(Suppl 8):S49-S55.Google Scholar
- 24.Samaha FF, Heineman FW, Ince C, Fleming J, Balaban RS. ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo.Am J Physiol 1992;262 (Cell Physiol 31):C1220-C1227.PubMedGoogle Scholar
- 25.Suryapranata H, Serruys PW. Coronary vasodilatory action after nicorandil: A quantitative angiographic study.Am J Cardiol 1989;63:80J-85J.PubMedGoogle Scholar