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Development of sensitve assay of NO and its clinical application

Research Project

Project/Area Number 07557055
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

HIRATA Yasunobu  Univ.of Tokyo, Medicine, Associate Prof., 医学付属病院, 講師 (70167609)

Co-Investigator(Kenkyū-buntansha) GYOUTOKU Yuichi  Ajinomoto Co., Central Research Institute, Chief, 所長
MABUCHI Kunihiko  Univ.of Tokyo, Research Center for Advanced Science and Technology, Prof., 先端科学技術センター, 教授 (50192349)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordsnitric oxide / chemiluminescence / inhalation / exhaled air / arteriosclerosis / kidney / 化学発光 / NO合成酵素
Research Abstract

The aims of the present study were development of highly sensitive NO assay system and its clinical application. We newly developed luminol chemiluminescence assay for NO and applied it to the rat isolated perfused kidney. Using this system, we found that endothelin-1 released NO through stimulation of ETB receptors and that this response was attenuated in the vessels with endothelial damage. Adrenomedullin, of which second messenger had been believed only cAMP,exhibited vasodilatory action by NO-cGMP system. Vasopressin increased NO release through V1 receptors. In particular, in arteriosclerotic vessels, NO may greatly influence a role of these vasoactive substances in regulation of vascular tone. We analyzed NO output in the exhaled air of patients with liver cirrhosis and renal failure by ozone chemiluminescence, and found the increase in NO excretion. Furthermore, we developed a fluorescein specifically sensitive to NO,and succeeded in bioimaging analysis of NO in the cultured cells and tissue slices. We also tried an NO inhalation therapy in patients with heart failure. Inhaled NO dilated pulmonary vessels without changes in systemic vasculature, resulting in an increase in gas exchange. Moreover, NO gas improved exercise capacity in these patients. These results suggest that NO inhalation may be useful for improvement of quality of life in heart failure.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hirata Y 他: "Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney" Hypertension. 29. 58-67 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikenouchi H, Hirata Y: "Negative Inotropic Effect of Adrenomedullin in Isolated Adult Rabbit Cardiac Ventricular Myocytes" Circulation. 95. 2318-2324 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matumoto A, Hirata Y: "Inhaled Nitric oxide and exercise capacity in congestive heart failure" Lancet. 349. 999-1000 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bremer V, Hirata Y: "Role of nitric oxide in rat nephrotoxic nephritis : Comparison between inducible and constitutive oxide synthase" J Am Soc Nephrol. 8. 1712-1721 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kojima h, Hirata Y: "Development of fluorescent indicator for the bioimaging of nitric oxide" Biol Pharma Bull. 20. 1229-1232 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimura K, Hirata Y: "Location and action of angiotensin II type 1 receptor in the renal microcirculation" Kidney Int. 63. S201-S204 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirata Y,Hayakawa H,Kakoki M,Tojo A,Suzuki E,Nagata D,Kimura K,Goto A,Kikuchi K,Nagano T,Hirobe M,Omata M.: "Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney." Hypertension. 29. 58-64 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikenouchi H,Kangawa K,Matsuo H,Hirata Y.: "Negative Inotropic Effect of Adrenomedullin in Isolated Adult Rabbit Cardiac Ventricular Myocytes." Circulation. 95. 2318-2324 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsumoto A,Momomura S,Hirata Y,Aoyagi T,Sugiura S,Omata M.: "Inhaled nitric oxide and exercise capacity in congestive heart failure." Lancet. 349. 999-1000 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bremer V,Tojo A,Kimura K,Hirata Y,Goto A,Nagamatsu T,Suzuki Y,Omata M.: "Role of nitric oxide in rat nephrotoxic nephritis : Comparison between inducible and constitutive nitric oxide synthase." J Am Soc Nephrol. 8. 1712-1721 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kojima H,Sakurai K,Kikuchi K,Kawahara S,Kirino Y,Nagoshi H,Hiarata Y,Akaike T,Maeda H,Nagano T.: "Development of fluorescent indicator for the bioimaging of nitric oxide." Biol Pharma Bull. 20. 1229-1232 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kojima H,Sakurai K,Kikuchi K,Kawahara S,Kirino Y,Nagoshi H,Hirata Y,Nagano T.: "Development of a fluorescent indicator for nitric oxide based on the fluorescein chromophore." Chem Pharma Bull. 46. 373-375 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirata Y他: "Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney" Hypertension. 29. 58-64 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikenouchi H,Hirata Y: "Negative Inotropic Effect of Adrenomedullin in Isolated Adult Rabbit Cardiac Ventricular Myocytes" Circulation. 95. 2318-2324 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsumoto A,Hirata Y: "Inhaled nitric oxide and exercise capacity in congestive heart failure" Lancet. 349. 999-1000 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bremer V,Hirata Y: "Role of nitric oxide in rat nephrotoxic nephritis : Comparison between inducible and constitutive nitric oxide synthase" J Am Soc Nephrol. 8. 1712-1721 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kojima H,Hirata Y: "Development of Fluorescent indicator for the bioimaging of nitric oxide" Biol Pharma Bull. 20. 1229-1232 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kimura K,Hirata Y: "Location and action of angiotensin II typeI receptor in the renal microcirculation" Kidney Int. 63. S201-S204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikenouchi Hiroshi: "Negative inotropic effect of adrenomedullin in isokated adult rabbit cardiac ventricular myocytes." Circulation. (印刷中).

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirata Yasunobu: "Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney." Hypertension. 29. 58-64 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Goto Atsuo: "Ouabain-like compound in hypertension associated with ectopic corticotropin syndrome." Hypertension. 28. 421-425 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kimura Kenjiro: "Hypertensive glomerular damage as revealed by the expression of α-smooth muscle actin and non-muscle myosin." Kidney Int. 49(suppl 55). S169-S172 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tojo Akihiro: "Effects of antihypertensive drugs on nitric oxide synthase activity in rat kidney." Kidney Int. 49(suppl 55). S138-S140 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirata Yasunobu: "Nitric oxide release from kidneys of hypertensive rats treated with imidapril." Hypertension. 27. 672-678 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirata Yasunobu: "Nitric oxide release from kidneys of hyperfensive rats treated with imidapril" Hypertension. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumoto Akihiro: "Increased nitric oxide in the exhaled air of patients with clecompensated liver cirrhosis" Ann Intern Med. 123. 110-113 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hayakawa Hiroshi: "Endo the lium-derived relaying factors in the kidney of spontaneously hypertensive rats" Life Sci. 56. PL401-PL408 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirata Yasunobu: "Mechanisms of adrenomedullin-induced vasodilation in the rat kidney" Hypertension. 25. 790-795 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirata Yasunobu: "Participation of endogenous ANP in regulation of urinary protein excretion in experimental diabetic rats" Clin Sci. 88. 413-419 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirata Yasunobu: "Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin raceptoers in rat Ridney" Cirwlation. 91. 1229-1235 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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