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1993 Fiscal Year Final Research Report Summary

Potential roles of K channels on coronary artery tone in vivo

Research Project

Project/Area Number 04670531
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionShiga University of Medical Science

Principal Investigator

KINOSHITA Masahiko  Shiga University of Medical Science First Iternal Medicine Professor, 医学部, 教授 (60093168)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Yishihisa  Shiga University of Medical Science First Iternal Medicine Assistant Professor, 医学部, 助手 (30216337)
TSUTAMOTO Takayoshi  Shiga University of Medical Science First Iternal Medicine Assistant Professor, 医学部, 助手 (40197695)
Project Period (FY) 1992 – 1993
Keywordscoronary artery / phasic contraotion / K^+ channel / glibenclamide
Research Abstract

To investigate the role of ATP-sensitive potassium chammel (ATP-K) in coronary arteries, we examined the effects of intravenous administration of glibenclamide (GLB, 0.3, 1.0, 3.0 mg/kg), a specific ATP-K blocker, in chronically instrumented dogs. Epicardial coronary artery diameter(CoD) and coronary blood flow (CBF) were measured continuously. Oscillations of CoD and CBF (phasic contractions) accurred in all of 6 dogs after injection of GLB (3mg/kg). CoD oscillated only slightly with a decrease by 2.3(〕SY.+-.〔)0.4 % ; CBF showed marked oscillation, with a peak flow rate of 21.9(〕SY.+-.〔)2.7ml/min(+26.6%) and atrough flow rate of 10.3(〕SY.+-.〔)2.9ml/min(-46.3%) (baseline flow was 17.8(〕SY.+-.〔)2.4 ml/min). GLB (1mg/kg) produced a slight decrease in CBF without oscillation, while GLB (0.3mg/kg)had almost no effect. These oscillations were not associated with a decrease in myocardial blood flow by the hydrogen gas clearance method. Nicrandil(0.2mg/kg), cromakalim (20 mug/kg) and diltiazem (0.2mg/kg) almost completely suppressed the oscillation, while nitroglycerin (15 mug/kg) did not. These findings suggest that ATP-K has an important in vivo role in modulating large and small coronary artery tone through activation of the voltage-dependent Ca channel.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 木之下正彦: "Pharmacology and therapeutic effects of nicorandil" Cardiovascular Drugs and Therapy. 4. 1075-1088 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本賢治: "Coronary effects of nicorandil in comparison with nitroglycerin in chronic concious dogs" Cardiovascular Drugs and Therapy. 5. 131-138 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中江一郎: "イヌの心外膜冠動脈と冠抵抗血管トーヌス調節におけるATP-sensitive potassium channelの関与" Therapeutic Research. 14. 87-97 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松本鉄也: "Mechanisms of Endo thelium-dependent responses to vasoactive agents in isolated porcine coronary arteries" J Cardiovasc Pharmacology. 228-234 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中江一郎: "Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia" J Cardiovasc Pharmacology. 23(予定). 473-479 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中江一郎: "Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs" Cardiovascular Drugs and Therapy. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiko Kinoshita: "Pharmacology and therapeutic effects of nicrandil" Cardiovasvular Drugs and Thrapy. Vol, 4. 1075-1088 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Hashimoto: "Coronary effects of nicorandil in comparison with notroglycerin in chronic concious dogs" Cardiovascular Drugs and Therapy. Vol.5. 131-138 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichiro Nakae: "Roles of ATP-sensitive Potassium Channel in Regulation of Tone of Canine Coronary Artery" Therapecutic Research. Vol.14. 87-97 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tetsuya Matsumoto: "Mechanisms of Endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries" J Cardilvasc Pharmacology. 228-234 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichiro Nakae: "Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia" J Cardiovasc Pharmacology. Vol.23. 473-479 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichiro Nakae: "Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs" Cardlovascular Drugs and Therapy. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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