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Pathophysiological and molecular pharmacological studies on the role of reactive oxygen species in disorder of circulatory function.

Research Project

Project/Area Number 11470514
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionNagoya City University

Principal Investigator

ITOH Takeo  Nagoya City University Medical School, Professor, 医学部, 教授 (70159888)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Seigo  Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (60079994)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥9,200,000 (Direct Cost: ¥9,200,000)
Keywordssuperoxide / reactive oxygen species / hydrogen peroxide / prostaglandin / vascular smooth muscle / endothelial cells / vasorelaxation / hyperpolarization
Research Abstract

The level of superoxide production was investigated by measuring lucigenin chemiluminescence signals in rabbit saphenous arteries with and without endothelium. Phorbol 12, 13-dibutirate (PDBu), an activator of protein kinase C (PKC), increased the chemiluminescence signals in preparations with and without endothelium. Under the conditions, superoxide dismutase(SOD) greatly attenuated the chemiluminescence signals. Each GF109203 (a selective inhibitor of PKC) and diphenylene iodochloride [an inhibitor of NAD (P) H oxidase] inhibited the chemiluminescence signals. These results suggest that an activation of NAD (P) H by PKC enhances generation of superoxide in vascular smooth muscle cells (and possibly in endothelial cells).
Superoxide generated by hypoxanthine + xanthine oxidase inhibited the contraction induced by noradrenaline (NAd) in endothelium-denuded strips of rabbit mesenteric arteries. This superoxide-induced response was enhanced by SOD, but this was inhibited by catalase or as … More corbic acid. These results suggest that under physiological conditions, SOD breaks down superoxide to H_2O_2 that inhibits the NAd-induced contraction in vascular smooth muscles.
H_2O_2 hyperpolarized smooth muscle cell membrane, which was inhibited by diclofenac sodium (an inhibitor of cyclooxygenase), and by glibenclamide (an inhibitor of K_<ATP> channels). These results suggest that H_2O_2 increases the synthesis of prostaglandins that hyperpolarizes the smooth muscle cell membrane through an activation of K_<ATP> channels. It is also suggested that the H_2O_2-induced membrane hyperpolarization plays an important role on the H_2O_2-induced relaxation on NAd-contraction in rabbit mesenteric artery.
In β-escin-skinned smooth muscles of rabbit mesenteric arteries, NAd plus GTP enhanced the contraction induced by 0.3 μM Ca^<2+>. H_2O_2 had no effect on the Ca^<2+>-contraction in the presence and absence of NAd plus GTP, suggesting that H_2O_2 has no direct action on the Ca^<2+>-sensitivity of contractile proteins in vascular smooth muscles of rabbit mesenteric artery. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Takayuki Asano: "Roles of epithelium on H_2O_2-induced inhibition of acetylcholine-contraction in rabbit intrapul-monary bronchiole"British Journal of Pharmacology. 132・6. 1271-1280 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seigo Fujimoto: "Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery"European Journal of Pharmacology. 412・3. 261-300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masuo Ohashi: "Possible mechanisms underlying the vasodilatation induced by olprinone, a phosphodiesterase III inhibitor, in rabbit coronary artery."British Journal of Pharmacology. 129・5. 1000-1006 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikatsu Suzuki: "Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia."British Journal of Pharmacology. 131・1. 37-42 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikatsu Suzuki: "Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia."Journal of Physiology. 527・1. 163-174 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikatsu Suzuki: "Modified histamine-induced NO-mediated relaxation in resistance arteries in pre-eclampsia."European Journal of Pharmacology. 410・1. 7-13 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takayuki Asano, Tomonori Hattori, Toyohiro Tada, Junko Kajikuri, Toshio Kamiya, Michihiro Saitoh, Yasuo Yamada, Makoto Itoh, Takeo Itoh.: "Role of the epithelium in opposing H_2O_2-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole."British Journal of Pharmacology. 132 (6). 1271-1280 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seigo Fujimoto, Takayuki Asano, Maiko Sakai, Keita Sakurai, Daisuke Takagi, Nobuyasu Yoshimoto, Takeo Itoh.: "Mechanism of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery."European Journal of Pharmacology. 412 (3). 291-300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masuo Ohashi, Yasuaki Dohi & Takeo Itoh.: "Possible mechanisms underlying the vasodilatation induced by olprinone, a phosphodiesterase III inhibitor, in rabbit coronary artery."British Journal of Pharmacology. 129 (5). 1000-1006 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikatsu Suzuki, Michihiro Saitoh, Kaoru Suzumori, Junko Kajikuri & Takeo Itoh.: "Characterization of changes in mechanical responses to histamine in omental resistance arteries in preeclampsia."British Journal of Pharmacology. 131 (1). 37-42 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikatsu Suzuki, Junko Kajikuri, Kaoru Suzumori & Takeo Itoh.: "Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia."Journal of Physiology. 527 (1). 163-174 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki Y.Yamamoto T, Suzumori K, Kajikuri J, and Itoh T.: "Modified histamine-induced NO-mediated relaxation in resistance arteries in pre-eclampsia."European Journal of Pharmacology. 410 (1). 7-13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takayuki Asano: "Roles of epithelium on H_2O_2-induced inhibition of acetylcholine-contraction in rabbit intrapulmonary bronchiole"British Journal of Pharmacology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seigo Fujimoto: "Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery"European Journal of Pharmacology. 412・3. 261-300 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 伊藤 猛雄: "硝酸薬の作用機序"医薬ジャーナル. 35・9. 2212-2220 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 伊藤 猛雄: "硝酸薬のすべて"エクセプタ・メディカ. 254 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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