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Role of Protein Kinases Phosphorylation in the Inhibitory Effect of Volatile Anesthetics on Vascular Smooth Muscle Contraction.

Research Project

Project/Area Number 16591557
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionWakayama Medical University

Principal Investigator

OGAWA Koji  Wakayama Medical University, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (30204077)

Co-Investigator(Kenkyū-buntansha) MIZUMOTO Kazuhiro  Wakayama Medical University, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (50239258)
HATANO Yoshio  Wakayama Medical University, Department of Anesthesiology, Professor and Chairman, 医学部, 教授 (70115913)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsAngiotensin II / Vascular smooth muscle / Sevoflurane / Isoflurane / Intracellular Ca^<2+> concentration / Protein kinases / プロポフォール / PKC
Research Abstract

This study was to investigate the effects of volatile anesthetics including sevoflurane and isoflurane on the expression of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), Rho-kinase and tyrosine kinase (TK) induced by angiotensin using Western blotting in isolated rat aorta.
1) Angiotensin II (Ang II) elicited a transient increase in muscle tension and intracellular calcium concentration [Ca^<2+>]1 in isolated rat aorta without endothelium. Western blotting revealed an increase in phosphorylated PKCα in response to Ang II.
2) Sevoflurane inhibited the muscle tension but not [Ca^<2+>]1 in response to Ang II in a concentration-dependent manner. Sevoflurane also attenuated Ang II-induced phosphorylation of PKCα. By contrast, Isoflurane, at clinically relevant concentrations, inhibited both muscle tension and [Ca^<2+>]1, but failed to affect the PKC phosphorylation in response to Ang II,
3) Ang II also stimulated the p44/42 MAPK phosphorylation in rat aorta, which was inhibi … More ted by sevoflurane in a concentration-dependent fashion.
4) GTPγS, a GTP analogue, stimulated Rho/Rho-kinase signaling pathway and induced vasoconstriction which was associated with membrane translocation of RhoA and Rock2. Sevoflurane attenuated both vascular contraction and activation of RhoA and Rock2 induced by GTPγS.
5) Sodium orthovanadate (Na_3VO_4), an inhibitor of protein tyrosine phosphatase, induced a sustained contraction of rat aorta and significant increase in protein tyrosine phosphorylation of a set of substrates including PLC-γ1 and P42 MAPK. Isoflurane suppressed Na_3VO_4-induced vascular contraction and the total density of the Na_3VO_4-induced, tyrosine-phosphorylated substrate bands including PLC-γ1 band and P42 MAPK band in a concentration-dependent manner.
6) Although sevoflurane also attenuated both vascular contraction and protein tyrosine phosphorylation in response to Na3V0.1, the extent induced by sevoflurane was less than that by sevoflurane at equi-potent concentrations.
These results suggested that the ability of volatile anesthetics including sevoflurane and isoflurane to alter the vascular smooth muscle tension appears to be modulated through different combinations of mechanisms, including Ca^<2+>-mediated pathways and Ca^<2+> sensitization, with exact combination depends on the anesthetic agent tested. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005 2004 Other

All Journal Article (25 results)

  • [Journal Article] The mechanism behind the inhibitory effect of isoflurane on Angiotensin II-induced contraction is different from that of sevoflurane.2007

    • Author(s)
      Ishikawa A, Ogawa K, Tokinaga Y, Uematsu N, Mizumoto K, Hatano Y
    • Journal Title

      Anesth Analg (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The mechanism behind the inhibitory effect of isoflurane on Angiotensi II-induced contraction is different from that of sevoflurane.2007

    • Author(s)
      Ishikawa A, Ogawa K, Tokinaga Y, Uematsu N, Mizumoto K, Hatano Y
    • Journal Title

      Anesth Analg (in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase Cmediated contraction of rat aortic smooth muscle.2006

    • Author(s)
      Yu J, Kakutani T, Mizumoto K, Hasegawa A, Hatano Y
    • Journal Title

      Acta Anesthesiol Scand 50

      Pages: 1131-1138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Propofo inhibits phorbol 12, 13-dibutyrate-induced, protein kinas C-mediated contraction of rat aortic smooth muscle.2006

    • Author(s)
      Yu J, Kakutani T, Mizumoto K, Hasegawa A, Hatano Y
    • Journal Title

      Acta Anaesthesiol Scand 50

      Pages: 1131-1138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated contraction of rat aortic smooth muscle.2006

    • Author(s)
      Yu J, Kakutani T, Mizumoto K, Hasegawa A, Hatano Y
    • Journal Title

      Acta Anesthesiol Scand 50

      Pages: 1131-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Vasodilation mediated by inward rectifier K^+ channels in cerebral microvessels of hypertensive and normotensive rats.2006

    • Author(s)
      Nakahata K, Kinoshita, H, Tokinaga Y, Ishida Y, Kimoto Y, Dojo M, Mizumoto K, Ogawa K, Hatano Y
    • Journal Title

      Anesth Analg 102

      Pages: 571-6

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Halothane does not protect against vascular injury in isolate cerebral and mesenteric arteries.2005

    • Author(s)
      Ogawa K, Tokinaga Y, Iwahashi S, Mizumoto K, Hatano Y
    • Journal Title

      Can J Anesth 52

      Pages: 870-877

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The inhibitory effects of sevoflurane on angiotensin II-induced, p44/42 mitogen-activated protein kinase-mediated contraction of rat aortic smooth muscle.2005

    • Author(s)
      Yu J, Mizumoto K, Kakutani T, Hasegawa A, Ogawa K, Hatano Y
    • Journal Title

      Anesth Analg 101

      Pages: 315-321

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparioson of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation-mediated vascular contraction.2005

    • Author(s)
      Yu J, Mizumoto K, Kakutani T, Hasegawa A, Ogawa K, Hatano Y
    • Journal Title

      Acta Anaesthesiol Scand 49

      Pages: 850-858

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sevoflurane enhances nitroglycerin tolerance in rat aorta : Implications for the desensitization of soluble guanylate cyclase possibly through the additive generation of superoxid anions and/or hydroxyl radicals within vascular smooth muscle2005

    • Author(s)
      Kakutani T, Ogawa K, Hatano Y, Mizumoto K, Iwahashi S
    • Journal Title

      Anesth Analg 101

      Pages: 1015-1022

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation-mediated vascular contraction.2005

    • Author(s)
      Yu J, Mizumoto K, Kakutani T, Hasegawa A, Ogawa K, Hatano Y
    • Journal Title

      Acta Anaesthesiol Scand 49

      Pages: 852-858

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The inhibitory effects of sevoflurane on angiotensin II-induced, p44/42 mitogen- activated protein kinase-mediated contraction of rat aortic smooth muscle.2005

    • Author(s)
      Yu J, Mizumoto K, Tokinaga Y, Ogawa K, Hatano Y
    • Journal Title

      Anesth Analg 101

      Pages: 315-321

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sevoflurane enhances nitroglycerin tolerance in rat aorta : Implications for the desensitization of soluble guanylate cyclase possibly through the additive generation of superoxide anions and/or hydroxyl radicals within vascular smooth muscle.2005

    • Author(s)
      Kakutani T, Ogawa K, Hatano Y, Mizumoto K, Iwahashi S
    • Journal Title

      Anesth Analg 101

      Pages: 1015-1022

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Halothane does not protect against vascular injury in isolated cerebral and mesenteric arteries.2005

    • Author(s)
      Ogawa K, Tokinaga Y, Iwahashi S, Mizumoto K, Hatano Y
    • Journal Title

      Can J Anesth 52

      Pages: 870-877

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of Ca^<2+> sensitization in ropivacaine-induced contraction of rat aortic smooth muscle.2005

    • Author(s)
      Yu J, Tokinaga Y, Kuriyama T, Mizumoto K, Hatano Y
    • Journal Title

      Anesthesiology 103

      Pages: 548-555

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparioson of the effects of isoflurane and sevoflurane on proteir tyrosine phosphorylation-mediated vascular contraction.2005

    • Author(s)
      Yu J, Mizumoto K, Kakutani T, Hasegawa A, Ogawa K, Hatano Y
    • Journal Title

      Acta Anaesthesiol Scand 49

      Pages: 852-858

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The inhibitory effects of sevoflurane on angiotensin II-induced, P44/4 mitogen-activated protein kinase-mediated contraction of rat aortic smooth muscle.2005

    • Author(s)
      Yu J, Mizumoto K, Tokinaga Y, Ogawa K Hatano Y
    • Journal Title

      Anesth Analg 101

      Pages: 315-321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sevoflurane enhances nitroglycerin tolerance in rat aorta : Implication for the desensitization of soluble guanylate cyclase possibly throug the additive generation of superoxide anions and/or hydroxyl radical within vascular smooth muscle.2005

    • Author(s)
      Kakutani T, Ogawa K, Hatano Y, Mizumoto K, Iwahashi S
    • Journal Title

      Anesth Analg 101

      Pages: 1015-1022

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Halothane does not protect against vascular injury in isolated cerebra and mesenteric arteries.2005

    • Author(s)
      Ogawa K, Tokinaga Y, Iwahashi S, Mizumoto K, Hatano Y
    • Journal Title

      Can J Anesth 52

      Pages: 870-877

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of Ca2+ sensitization in ropivacaine-induced contractio of rat aortic smooth muscle.2005

    • Author(s)
      Yu J, Tokinaga Y, Kuriyama T, Uematsu N, Mizumoto K, Hatano Y
    • Journal Title

      Anesthesiology 103

      Pages: 548-555

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sevoflurane Inhibits Angiotensin II-induced, Protein Kinase C-mediated but Not Ce2^<+>-elicited Contraction of Rat Aortic Smooth Muscle.2004

    • Author(s)
      Yu J, Tokinaga Y, Ogawa K, Iwahashi S, Hatano Y
    • Journal Title

      Anesthesiology 100

      Pages: 879-884

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The vascular relaxing effects of sevoflurane and isoflurane are more important in hypertensive than in normotensive rats.2004

    • Author(s)
      Yu J, Ogawa K, Tokinaga Y, Iwahashi S, Hatano Y
    • Journal Title

      Can J Anesth 51

      Pages: 979-985

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] The Inhibitory effects of isoflurane on protein tyrosine phosphorylation-modulated contraction of rat aortic smooth muscle.2004

    • Author(s)
      Yu J, Ogawa K, Tokinaga Y, Mizumoto K, Kakutani T, Hatano Y
    • Journal Title

      Anesthesiology 101

      Pages: 1325-1331

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Sevoflurane Inhibits Angiotensin II-induced, Protein Kinase C-mediated but Not Ca^<2+>-elicited Contraction of Rat Aortic Smooth Muscle.2004

    • Author(s)
      Yu J, Tokinaga Y, Ogawa K, Iwahashi S, Hatano Y
    • Journal Title

      Anesthesiology 100

      Pages: 879-884

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The mechanism behind the inhibitory effect of isoflurane on Angiotensin II-induced contraction is different from that of sevoflurane.

    • Author(s)
      Ishikawa A,.0gawa K, Tokinaga Y, Uematsu N, Mizumoto K, Hatano Y
    • Journal Title

      Anesth Analg 2007 (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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