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

Research Project

Project/Area Number 06670725
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

EGASHIRA Kensuke  Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60260379)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsATP-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.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [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
    • Related Report
      1995 Final Research Report Summary
  • [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
    • Related Report
      1995 Final Research Report Summary
  • [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
    • Related Report
      1995 Final Research Report Summary
  • [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
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Katsuda Y. et al.: "Glibenclamaide, a selective inhibitor of ATP-sensitive K channels attenuates. metabolic coronary vasodilation induced by pacing tachycardia in dogs." Circulation. 92. 511-517 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Katsuda Y. et al.: "ATP-sensitive potasium channel opener pinacidil augments b-1 selective adrenoceptor induced coronary vasodilation in dogs." American Journal of Physiology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Narisige T.: "Glibenclamide prevents coronary vasodilation induced by beta-1 adrenoceptor stimulation in dogs." American Journal of Physiology. 266,H35. H84-H92 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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