THE ROLE OF ATP-SENSITIVE POTASSIUM CHANNELS IN THE MECHANISMS OF METABOLIC CORONARY VASODILATION

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06670725
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: EGASHIRA Kensuke Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60260379)
• Project Period (FY): 1994 – 1995
• Keywords: ATP-sensitive potassium channels / coronary circulation / metabolic coronary vasodilation / glibenclamide / dogs

Research Abstract

1) Effects of glibenclamide (an inhibitor of ATP-sensitive potassium channels) on metabolic coronary vasodilation
Experiments were performed in anesthetized and conscious dogs. Increasing heart rate from 100 to 160 bpm increased coronary blood flow without altering other hemodynamic parameters. Glibenclamide (1.5 and 5.0 mug/kg・min) significantly inhibited coronary vasodilation induced by pacing tachycardia, while it did not affect coronary vasodilation induced by acetylcholine and nitroglycerin. Glibenclamide completely abolished coronary vasodilation induced by pinacidil. These results suggest that metabolic coronary vasodilation is mediated at least in part by ATP-sensitive potassium channels.
2) Effects of Pinacidil (ATP-sensitive potassium channel opener) on metabolic coronary vasodilation
Experiments were performed in anesthetized dogs. Intracoronary infusion of denopamine (a selective beta1-adrenoceptor agonist) increased coronary blood flow associated with an increase in myocardial inotropic state. Pinacidil 1 mug/min, that had no effects on basal hemodynamic parameters but modestly increased coronary blood flow by 10% or less, augmented coronary vasodilation induced by denopamine, while denopamine-induced changes in myocardial inotropic state and myocardial oxygen consumption were comparable before and after pinacidil.Pinacidil did not affect coronary vasodilation induced by acetylcholine, nitroglycerin, and beta2-adrenoceptor stimulation. Denopamine-induced coronary vasodilation was completely inhibited by a selective beta1 adrenoceptor antagonist bisoprolol. These results suggest that ATP-sensitive potassium channel opener pinacidil augments metabolic coronary vasodilation induced by beta1-adrenoceptor stimulation.

Research Products

• [Publications] Katsuda Y., et al: "Glibenclamide, a selective inhibitor of ATP-sensitive K channels attenuates metabolic coronary vasodilation induced by pacing tachycardia in dogs." Circulation. 92. 511-517 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Katsuda Y., et al: "ATP-sensitive potasium channel opener pinacidil augments b-1 selective adrenoceptor induced coronary vasodi lation in dogs." American Journal of Physiology. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] KATSUDA.Y, EGASHIRA.K, UENO.H, AKATSUKA.Y, NARISHIGE.T, ARAI.Y, TAKAYANAGI.T, SHIMOKAWA.H, TAKESHITA.A.: "GLIBENCLAMIDE, A SELECTIVE INHIBITOR OF ATP-SENSITIVE POTASSIUM CHANNELS, ATTENUATES METABOLIC CORONARY VASODILATION INDUCED BY PACING TACHYCARDIA IN DOGS." CIRCULATION. 92. 511-517 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] KATSUDA.Y, EGASHIRA.K, UENO.H, ARAI.Y, AKATSUKA.Y, KUGA.T, SHIMOKAWA.H, TAKESHITA.A.: "ATP-SENSITIVE POTASSIUM CHANEL OPENER PINACIDIL AUGMENTS b1-ADRENOCEPTOR-INDUCED CORONARY VASODILATION IN DOGS." AMJ PHYSIOL. (IN PRESS).
  • Description: 「研究成果報告書概要(欧文)」より