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A Study on the Effect of Nitric Oxide on Myocardial Oxygen Consumption and Cardiac Contractility

Research Project

Project/Area Number 10670623
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OKUMURA Ken  Hirosaki University, Department of Medicine, Professor, 医学部, 教授 (20185549)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsnitric oxide / cardiac contractility / Emax / coronary blood flow / FK409 / Papaverine / cyclic GMP
Research Abstract

We have shown that inhibition of endogenous nitric oxide (NO) augments cardiac contractility assessed by Emax, whereas others showed that spontaneous NO donors evoke a positive inotropic effect. FK409 decomposes and releases NO spontaneously when dissolved in phosphate buffer solution at 37℃. We examined the effects of FK409 and 8-bromoguanosine-cyclic-monophosphate (8-Br-cGMP) on Emax in α-chloralose-anesthetized dogs instrumented for measurements of left ventricular (LV) pressure and volume and coronary blood flow (CBF) in the left anterior descending artery (LAD). FK409, 8-Br-cGMP or papaverine was infused into the LAD, and Emax was determined by transient inferior vena cava occlusion when CBF was increased and reached its peak. Neither drug affected heart rate or LV pressure just before the measurement of Emax. FK409 increased CBF and decreased Emax in a dose-dependent manner. 8-Br-cGMP increased CBF and decreased Emax in a dose-dependent manner. Papaverine increased mean CBF but did not affect Emax. In conclusion, NO attenuates cardiac contractility in vivo, while increasing CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second messenger of NO.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Ken Okumura et al.: "Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency"Am.J.Physiol.. 275. H41-H49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura et al.: "A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility"Fundam.Clin.Pharmacol.. 13. 34-42 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura et al.: "Nitric oxide-dependent vasodilator mechanism is not impaired by hypertension but is diminished with aging in the rat aorta"J.Cardiovac.Pharmacal.. 33. 756-761 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura et al.: "Significance of sympathetic nervous system in sodiumiduced nocturnal hypertension"Journal of Hypertension. 17. 947-957 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura et al.: "Cross Talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells"Am.J.Physiol.. 278. H233-H238 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura et al: "Study on the relationship between plasma nitric and nitrate level and salt sensitivity in human hypertension"Circulation. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishizaka K, Okumura K, Yamabe H, et al.: "J Cardiovasc Pharmacol"J Cardiovasc Pharmacol. 18. 665-669 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamabe H, Okumura K, Ishizaka H, et al.: "Role of endothelium-derived nitric oxide in myocardial reactive hyperemia."Am J Physiol. 263. 752-758 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsunoda R, Okumura K, Ishizaka H, et al.: "Influence of the inhibition of endothelium-derived nitric oxide formation to the effects vasoconstrictor agents, neuropeptide Y, clonidine and ergonovine and ergonovine, on coronary vascular resistance."J Cadiovasc Pharmacol. 24. 87-94 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsunoda R, Okumura K, Ishizaka H, et al.: "Vasodilator effect of cardoxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-0xyl in the coronary circulation. In vivo and in vitro studies."Eur J Pharmacol. 262. 55-63 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsunaga T, Okumura K, Ishizaka H, et al.: "Effect of cumulative dose of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs."Arch Int Pharmacody. 327. 251-265 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okumura K, Yasue H, Fujii H, et al.: "Effects of brain (B-type) natriuretic peptide on coronary artery diameter and coronary hemodynamic variables in humans : Comparison with effects on systemic hemodynamic variables."J Am Coll Cardiol. 25. 342-348 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsunaga T, Okumura K, Tsunoda R, et al.: "Role of adenosine in regulation of coronary flow in dogs with inhibited synthesis of endothelium-derived nitric oxide."Am J Physiol. 270. H427-H434 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsunoda R, Okumura K, Ishizaka I, et al.: "Enhancement of myocardial reactive hyperemia with manganese-superoxide dismutase : role of endothelium-derived nitric oxide"Cardiovasc Res. 31. 537-545 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsunaga T, Okumura K, Ishizaka I, et al.: "Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in alloxan-induced diabetic dogs."J Cardiovasc Pharmacol. 28. 60-67 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okumura K, Yasue H, Matsuyama K, et al.: "Diffuse disorder of the coronary artery vasomotility in patients with coronary spastic angina. Hyperreactivitiy to acetylcholine's onstrictor and nitroglycerin's dilator effect."J Am Coll Cardio. 27. 45-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tayama S, Okumura K, Matsunaga T, et al.: "Influence of chronic nitric oxide inhibition to coronary blood flow regulation. A study on a role of endogenous adenosine in anesthetized, open-chest dogs."Jpn Circ J. 62. 371-378 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto N, Okumura K, Okubo T, et al.: "Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficacy."Am J Physiol. 275. H41-H49 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osanai T, Kamada T, Okumura K, et al.: "A novel inhibitory effect on prostacyclin synthesis of coupling factor 6 extracted from the heart of spontaneously hypertensive rats."J Biol Chem. 27. 31778-31783 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okubo T, Suto N. Okumura K, et al.: "A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility."Fundam Clin Pharmacol. 13. 34-42 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imaoka Y, Osanai T, Okumura K, et al.: "Nitric oxide-dependent vasodilator mechanism is not impaired by hypertension but is diminished with aging in the rat aorta."J Cardiovasc Pharmacol. 33. 756-761 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kaizuka M, Yamabe H, Okumura K, et al.: "Thrombin stimulates synthesis of type IV collagen and tissueinhibitor of metalloproteinases-1 by cultured human mesangial cells."J Am Soci Nephrol. 10. 1516-1523 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Guan W. Osanai T, Okumura K, et al.: "Time course of free radical production after primary coronary angioplasty for acute myocardial infarction and the effect of vitamin C."Jpn Circ J. 63. 924-928 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okuguchi T, Osanai T, Okumura K, et al.: "Significance of sympathetic nervous system in sodium-induced nocturnal hypertension."J Hypertension. 17. 947-957 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimura M, Osanai T, Okumura K, et al.: "Involvement of phosphorylation of β-subunit in cAMP-dependent activation of L-type CaィイD12+ィエD1 channel in aortic smooth muscle-derived A7r5 cells."Cellular Signalling. 12. 63-70 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osanai T, Okuguchi T, Okumura K, et al.: "Salt-induced exacerbation of morning surge in blood pressure in patients with essential hypertension."J Human Hypertension. 14. 57-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osanai T, Fujita N, Okumura K, et al.: "Cross talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells."Am J Physiol. 278. H233-H238 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujiwara N, Osanai T, Okumura K, et al.: "Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension. Modulation of nitric oxide synthesis by salt intake."Circulation. 101. 856-861 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ken Okumura, et al.: "Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency"Am.J.Physiol.. 275. H41-H49 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura, et al.: "A study on the effects of endogenous nitric oxide on coronary blood flow,myocardial oxygen extraction and cardiac contractility"Fundam.Clin.Pharmacol.. 13. 34-42 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura, et al.: "Nitric oxide-dependent vasodilator mechanism is not impaired by hypertension but is diminished with aging in the rat aorta"J.Cardiovasc.Pharmacal.. 33. 756-761 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura, et al.: "Significance of sympathetic nervous system in sodiumiduced nocturnal hypertension"Journal of Hypertension. 17. 947-954 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura, et al.: "Cross Talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells"Am.J.Physiol.. 278. H233-H238 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura, et al.: "Study on the relationship between plasma nitric and nitrate level and salt sensitivity in human hypertension"Circulation. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken Okumura.: "Nitric oxide modulates cardiac contractility and oxygen consumotion without changing contractile efficiency" Am.J.Physiol.275. H41-H49 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken Okumura.: "Influence of chronic nitric oxide inhibition of coronary blood flow regulation" Jpn Circ J. 62-5. 371-278 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken Okumura.: "A novel inhibitory effect on prostacyclin synthesis of coupling factor 6 extracted from the heart of spontaneously hypertensive rats" J Biol Chem. 273-48. 31778-31783 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken Okumura.: "Nitric oxide (NO) attenuates cardiac contractility assessed by emax in the dog heart:A study with a spontaneous no donor" Circulation. 98-17. I257 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken Okumura.: "A study on the effects of endogenous nitric oxide on coronary blood flow,myocardial oxygen extraction and cardiac contractility" Fundam Clin Pharmacol. 13. 34-42 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken Okumura.: "Nitric oxide-dependent vasod lator mechanism is not impaired by hypertension but is diminished with aging in the rat aorta" J Cardiovasc Pharmacal. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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