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Mechanisms of inhibition by volatile anesthetics on beta-adrenoceptor-mediated relaxation in the vascular smooth muscle

Research Project

Project/Area Number 08671760
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionSapporo Medical University School of Medicine

Principal Investigator

TSUCHIDA Hideaki  Sapporo Medical University, School of Medicine, M.D., 医学部, 講師 (20155394)

Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
KeywordsVolatile anesthetics / Vascular smooth muscle / Beta adrenergic receptor / nitroglycerin / Cytosolic concentration of Calcium ion / βアドレナリン受容体作動薬 / カルシウムイオン
Research Abstract

This study was designed to determine whether the volatile anesthetics halothane and isoflurane inhibit beta-adrenoceptor-mediated responses, and which signal transduction steps are important for the inhibition if they do. We found that the volatile anesthetics used at clinically relevant concentrations can interfere with responses mediated by the beta-adrenoceptor agonist, isoproterenol. Halothane and isoflurane impaired isoproterenol-induced vasodilation and a decline of cytosolic concentrations of Ca^<2+> ([Ca^<2+>]i), whereas they only slightly affected vasodilation induced by the adenylyl cyclase activator, forskolin, and the membrane-permeable cyclic AMP, dbcAMP.This finding is consistent with the additional result that both anesthetics inhibited isoproterenol-induced, but not forskolin-induced, increases in cyclic AMP contents. Furthermore, both agents did not interfere with the ligand-binding property to the beta-adrenoceptor. These results indicate that halothane and isoflurane predominantly interfere with beta-adrenoceptor-mediated responses at the step between the beta-adrenoceptor and adenylyl cyclase ; the logical site would therefore include Gproteins.
In addition to the vasorelaxation mediated by the beta-adrenoceptor-cyclic AMP system, we also investigated the effect of halothane on the vasorelaxation mediated by the nitric oxide (NO)-cyclic GMP system. We used nitroglycerin as a NO donor. We found that halothane interfered with nitroglycerin-induced vasorelaxation in a concentration-dependent fashion. Furthermore, halothane's inhibition was govemed by both [Ca^<2+>]i-dependent and [Ca^<2+>]i-independent mechanisms.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Tanaka S,Tsuchida H: "Effects of halothane and isoflurane on β-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta" Anesthesiology. 89. 1209-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuchida H,Tanaka S,et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta" Anesth Analg. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka S,Tsuchida H,et al.: "The effects of sevoflurane, isoflurane, halothane, and enflurane on hemodynamic responses during an inhaled induction of anesthesia via mask in humans." Anesth Analg. 82. 821-6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuchida H,et al.: "Sigma receptor activation does not mediate fentanyl-induced attenuation of muscarinic contraction." Anesth Analg. 82. 982-7 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Namba H,Tsuchida H: "Effect of volatile anesthetics with and without verapamil on intracellular activity in vascular smooth muscle." Anesthesiology. 84. 1365-74 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamakage M,et al.: "Role of intracellular Ca^<2+> stores in the inhibitory effect of halothane on airway smooth muscle contraction." Anesthesiology. 89. 149-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka S, Tsuchida H.: "Effects of halothane and isoflurane on beta-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta" Anesthesiology. 89. 1209-17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuchida H, Tanaka S, et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta" Anesth Analg. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka S, Tsuchida H, et al.: "The effects of sevoflurane, isoflurane, halothane, and enflurane on hemodynamic responses during an inhaled induction of anesthesia via mask in humans." Anesth Analg. 82. 821-6 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuchida H, et al.: "Sigma receptor activation does not mediate fentanyl-induced attenuation of muscarinic contraction." Anesth Analg. 82. 982-7 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Namba H, Tsuchida H.: "Effect of volatile anesthetics with and without verapamil on intracellular activity in vascular smooth muscle." Anesthesiology. 84. 1365-74 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamakage M, et al.: "Role of intracellular Ca^<2+> stores in the inhibitory effect of halothane on airway smooth muscle contraction." Anesthesiology. 89. 149-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka S,Tsuchida H: "Effects of halothane and isoflurane on β-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta" Anesthesiology. 89(5). 1209-1217 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuchida H,Tanaka S,et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta." Anesthesia & Analgesia. in press.

    • Related Report
      1998 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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