Mechanisms of vasodilation of cerebral vessels induced by the potassium channel opener nicorandil in canine in vivo experiments.

Abstract

Nicorandil, a potent antianginal agent characterized as a potassium channel opener, could produce cerebrovascular dilation in in vitro studies. Our aim was to investigate the pharmacologic response to the topical application of nicorandil on the vasomotor tone of pial vessels in vivo. To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation. In 14 dogs prepared with a parietal cranial window, we administered five different concentrations of nicorandil solution (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) mol/L) under the window and measured pial arterial and venular diameters. After pretreating pial vessels with either 10(-5) mol/L methylene blue or 10(-5) mol/L glibenclamide, we examined inhibitory action after the application of 10(-5) mol/L nicorandil. In additional experiments with 9 dogs, we evaluated the effects of nitroglycerin and cromakalim on pial vessels in the absence or presence of 10(-5) mol/L methylene blue and 10(-5) mol/L glibenclamide, respectively. Nicorandil produced significant, concentration-dependent dilation of pial vessels (P < .05). Methylene blue blocked nicorandil-induced dilation, whereas glibenclamide only attenuated such action of nicorandil. Nitroglycerin and cromakalim also produced a concentration-dependent increase in pial arteriolar and venular diameters (P < .05), and those effects were blocked in the presence of methylene blue or glibenclamide, respectively. Our in vivo study demonstrates that topical application of nicorandil dilates both pial arterioles and venules in a concentration-dependent manner and suggests that the mechanisms of such actions are most likely due to both cyclic GMP-mediated vascular smooth muscle dilation and the regulation of K+ flux.

Hyperthermia-Induced Vasoconstriction of the Carotid Artery and the Role of Potassium Channels

“…11 K-channels contribute to membrane potential in cerebral vessels. [12][13] Our hypothesis in this study was that hyperthermia inhibits K channels in smooth muscle cells of the carotid arteries, causing depolarization and vasoconstriction.…”

Mechanisms Underlying Cerebrovascular Effects of Cigarette Smoking in Rats In Vivo

“…22,23 The opening of such channels in the vascular smooth muscle cell causes vasorelaxation. 24 The complete inhibition of smokinginduced pial vasodilation by glibenclamide, a putative ATPsensitive K ϩ channel blocker, 25 suggests that this response is probably induced via an activation of ATP-sensitive K ϩ channels in the cerebral arterioles.…”

“…25 Indeed, we have previously demonstrated that topical application of glibenclamide can effectively block cromakalim-induced pial arteriolar and venular dilation in the dog in vivo. 22 In rat studies, the following occurred: (1) 20 mg/kg of glibenclamide given intravenously blunted the vasodilator effect of the K ϩ channel opener, diazoxide, but not that of the L-type Ca 2ϩ channel blocker, nicardipine, 26 and (2) 20 to 30 mg/kg of glibenclamide given intravenously inhibited the vasorelaxant Propranolol 132Ϯ4 136Ϯ7 145Ϯ10 151Ϯ10 134Ϯ5 124Ϯ12 124Ϯ8 128Ϯ5 129Ϯ4 125Ϯ3 L-NAME 125Ϯ5* 142Ϯ8 152Ϯ11 157Ϯ12 † 146Ϯ9 137Ϯ8 136Ϯ7 138Ϯ5 138Ϯ5 146Ϯ6 Glibenclamide 121Ϯ8 132Ϯ6 137Ϯ6 142Ϯ9* 135Ϯ6 133Ϯ5 132Ϯ5 129Ϯ4 129Ϯ4 127Ϯ5 Seratrodast 118Ϯ5 125Ϯ5 143Ϯ5* 163Ϯ5 † 128Ϯ5 124Ϯ5 124Ϯ5 127Ϯ5 126Ϯ4 122Ϯ5 HR, bpm…”

Cerebral Pial Vascular Changes Under Propofol or Sevoflurane Anesthesia During Global Cerebral Ischemia and Reperfusion in Rabbits

“…[5][6][7][8] Pial arterioles are important because they reflect cerebral blood flow. [5][6][7][8] Pial arterioles are important because they reflect cerebral blood flow.…”