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Abnormal intracellular CaィイD12+ィエD1 handling in heart failure ; effects of ACE inhibitor

Research Project

Project/Area Number 09670689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

TOMITA Fumishi  Hokkaido Univ., School of Med., Inst., 医学部, 助手 (40271655)

Co-Investigator(Kenkyū-buntansha) HATTORI Yuichi  Hokkaido Univ., School of Med., Asso. Pro., 医学部, 助教授 (50156361)
KOHYA Tetsuro  Hokkaido Univ. Medical Hospital, Lec., 医学部・附属病院, 講師 (70205350)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordscongestive heart failure / myocardial infarction / intracellular CaィイD12+ィエD1 handling / CaィイD12+ィエD1 sensitivity / ACE inhibitor / 細胞内Ca^<2+>ハンドリング
Research Abstract

We used the left coronary artery-ligated rat model of congestive heart failure. Left ventricular myocardial infarction (MI) was produced by ligation of the left coronary artery in Wistar-Kyoto rats at 10-12 weeks of age. Age-matched control rats underwent operation without coronary artery ligation (sham-operated control rats). ACE inhibitor therapy was begun 1 week after operation and was continued until week 6 after operation, when animal killed. To study the cellular mechanisms of the effects of ACE inhibition on the modification of the transition to failure in rat MI, we measured simultaneous intracellular CaィイD12+ィエD1 transients and myocyte shortening in isolated left ventricular myocytes from ACE-inhibitor treated MI rats, untreated MI rats, and sham-operated control rats. Collagenase-dissociated myocytes were loaded with indo 1-AM. In myocytes from untreated MI rats, the time to peak tension and the time to peak light were longer than those in the control. However, peak tension development and peak light, normalized for cell capacitance, were not different in the control and untreated MI. ACE inhibitor treatment improved the time course of both intracellular CaィイD12+ィエD1 transients and myocyte shortening. Maximal CaィイD12+ィエD1-activated force and CaィイD12+ィエD1 sensitivity of contractile protein were not different among the three groups. The present results indicate that ACE inhibitor-treatment improves the time course of intracellular CaィイD12+ィエD1 transients and myocyte shortenig in MI rats. This may contribute to the favorable effects whereby ACE inhibition modifies the transition from compensatory hypertrophy to failure.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Fumishi Tomita: "Different regulation of myofilament Ca^<2+> sensitivity in β-escin-skinned cardiac and vascular smooth muscles"Eur J Pharmacol. 326. 157-162 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mitsuhide Ohtsubo: "Metabolic abnormality of calf skeletal muscle is improved by localized muscle training without changes in blood flow in chronic heart failure"Heart. 78. 437-443 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hisashi Yokoshiki: "Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy"J Mol Cell Cardiol. 29. 1331-1339 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuhiro Akaishi: "Agonist-independent tonic inhibitory influence of Gi of adenyl cyclase activity in rabbit ventricular myocardium and its removal by pertussis toxin: a role of empty receptor-mediated Gi activation"J Mol Cell Cardiol. 29. 765-775 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Motoi Sasaki: "Tyrosine phosphorylation as a convergent pathway of heterotrimeric G protein and rho protein-mediated Ca^<2+> sensitization of smooth muscle of rabbit mesenteric artery"Br J Pharmacol. 125. 1651-1660 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koichi Okita: "Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure"Circulation. 98. 1886-1891 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fumishi Tomita, et al.: "Different regulation of myofilament CaィイD12+ィエD1 sensitivity in β-escin-skinned cardiac and vascular smooth muscles"Eur J Pharmacol. 326. 157-162 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mitsuhide Ohtsubo, et al.: "Metabolic abnormality of calf skeletal muscle is Improved by localized muscle training without changes in blood flow in chronic heart failure"Heart. 78. 437-443 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hisashi Yokoshiki, et al.: "Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy"J Mol Cell Cardiol. 29. 1331-1339 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuhiro Akaishi, et al.: "Agonist-independent tonic inhibitory influence of Gi of adenyl cyclase activity in rabbit ventricular myocardium and its removal by pertussis toxin : a role of empty receptor-mediated Gi activation"J Moll Cell Cardiol. 29. 765-775 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Motoi Sasaki, et al.: "Tyrosine phosphorylation as convergent pathway of heterotrimeric G protein- and rho protein-mediated CaィイD12+ィエD1 sensitization of smooth muscle of rabbit mesenteric artery"Br J Pharmacol. 125. 1651-1660 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koichi Okita, et al.: "Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure"Circulation. 98. 1886-1891 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koichi Okita: "Skeletal muscle metabolism in maximal bicycle and treadmill exercise distinguished by using in vivo metabolic freeze method and phosphorus-31 magnetic resonance spectroscopy in normal men." Am J Cardiol. 81. 106-109 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuko Kawai: "Use of ^<123>I-BMIPP single-photon emission tomography to estimate areas at risk following successful revasculatization in patients with acute myocardial infarction." Eur J Nucl Med. 25. 1390-1395 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koichi Okita: "Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure." Circulation. 98. 1886-1891 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Motoi Sasaki: "Tyrosine phosphorylation as a convergent pathway of heterotrimeric G-protein-and rho proteinmediated Ca^<2+> sensitization of smooth muscle of rabbit mesenteric artery." Br J Pharmacol. 125. 1651-1660 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fumishi Tomita: "Different regulation of myofilament Ca^<2+> sensitivity in β-escin-skinned cardiac and vascular smooth muscles." Eur.J.Pharmacology. 326. 157-162 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hisashi Yokoshiki: "Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy." J.Mol.Cell Cardiol.29. 1331-1339 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mitsuhide Ohtsubo: "Metabolic abnormality of calf skeletal muscle is improved by localized muscle training without changes in blood flow in chronic heart failure." Heart. 78. 437-443 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takafumi Motizuki: "Sequential change of BMIPP uptake in spontaneously hypertensive rat model." Ann.Nucl.Med.11. 299-306 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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