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Possible Mechanisms of Age-associated Decrease in Vascular Functions

Research Project

Project/Area Number 63571045
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, University of Tokushima

Principal Investigator

MORITOKI Hideki  Faculty of Pharmaceutical Sciences, University of Tokushima, Professor, 薬学部, 教授 (10035545)

Co-Investigator(Kenkyū-buntansha) HORIO Shuhei  Faculty of Pharmaceutical Sciences, University of Tokushima, 薬学部, 助手 (80145010)
FUKUZAWA Kenji  Faculty of Pharmaceutical Sciences, University of Tokushima, Associate Professor, 薬学部, 助教授 (90035551)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsAging / Vascular function / Vascular endothelium / Vasodilation / Cyclic GMP / Antiaggregating activity / Phosphodiesterase / Vitamin E / サイクリック ヌクレオチド / ホスフォジエステラ-ゼ / 過酸化脂質 / 血管内皮細胞 / 血管灌流 / 抗血小板凝集活性 / 血管拡張アセチルコリン / ATP / プロスタサイクリン
Research Abstract

The effect of aging on vascular functions were examined.
Aging reduced the endothelium-dependent dilator responses of rat thoracic aorta to vasodilators, such as acetylcholine, histamine, ATP and adenosine. Loss of the dilator responses was found to be associated with reduction of cGMP formation. These changes may be due to both reduction in ability of the endothelium to produce endothelium-derived relaxing factor (EDRF) and/or prostacyclin, and also decrease in guanylate cyclase activity.
The inhibitory effects of the cGMP-phosphodiesterase inhibitors M&B 22948 and dipyridamole on the phenylephrine-induced contraction, and accumulation of cGMP in the presence of M&B 22948 were greater in the arteries from old rats than those from young rats. These results suggest that with increase in age, hydrolysis of cGMP by cGMP-phosphodiesterase is accelerated, thus decreasing cGMP-dependent dilator response.
In the case of adenosine, specific binding sites of [^3H]NECA, a A2-adenosine receptor liga … More nd, decreased during aging. Reduction of the number of adenosine receptors in vascular smooth muscle could be responsible for the age-associated reduction of the dilator response and cGMP formation.
In addition to these changes, the activity of the endothelium to prevent platelet aggregation was also shown to be lower in the arteries from old rats. When the lumen of the arteries was perfused with Krebs solution containing acetylcholine, histamine or ATP, the luminal perfusate of the arteries from young rats effectively inhibited ADP-induced aggregation. The results suggest that the endothelium produces some anti-aggregating substance, probably prostacyclin, and that production of this substance decreases during aging.
A preliminary study on the effect of vitamin E deficiency and supplement on the responses of rat arteris to vasodilators was carried out. VE deficiency accelerated the age-associated decrease in dilator responses, whereas VE supplement protected the arteries from this change. Less

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Moritoki,H.,Tanioka,A.,Maeshiba,Y.,Iwamoto,T.,Ishida,Y.& Araki,H.: "Age-associated decrease in histamine-induced vasodilatation may be due to reduction of cyclic GMP formation." Brit.J.Pharmacol.95. 1015-1022 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Matugi,T.,Takase,H.,Ueda,H.,& Tanioka,A.: "Evidence for the involvement of cyclic GMP in adenosine-induced age-dependent vasodilation." Brit.J.Pharmacol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Yoshikawa,T.,Hisayama,T.& Takase,H.: "Contribution of the endothelial function to vasodilator effect of atrial natriuretic peptide"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Tanioka,A.Ueda,H.& Matsugi,T.: "Adenosini-induced vasodilaltion is mediated by cGMP.in:Bioinformatics" Eds.Hatase & Wong,Elsevier,Amsterdam, 251-254 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Tanioka,A.Ueda,H.: "Does cGMP mediate adenosine-induced vasodilation? in:Biosignaling in Cardiac and Vascular systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 292-295 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Tanioka,A.Matsugi,T.& Takase,H.: "Indicaktion of possible association of decrease in cGMP mediated vaso-dilation with increase in cGMP-phosphodiesterase activity during aging.:in Biosignaling in Cardiac and Vasculal Systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 288-291 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Tanioka,A.Ueda,H.: "Possible mechanisms of age-associated changes in vascular functtion.in:Biosignaling in Cardiac and Vascular Systems" Eds.Fujiwara et al.,Pergamon Press, Oxford, 284-287 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Tanioka, A., Maeshiba, Y., Iwamoto, T., Ishida, Y. & Araki, H.: "Age-associated decrease in histamine-induced vasodilatation may be due to reduction of cyclic GMP formation." Brit.J.Pharmacol.95. 1015-1022 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Matsugi, T., Takase, H., Ueda, H. & Tanioka, A.: "Evidence for the involvement of cyclic GMP in adenosine-induced age-dependent vasodilation." Brit.J.Pharmacol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Tanioka, A. Ueda, H. & Matsugi, T.: "Adenosine-induced vasodilatation is mediated by cGMP." Bioformatics. Eds.Hatase & Wong, Elsevier, Amsterdam. 251-254 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Tanioka, A. & Ueda, H.: "Does cGMP mediate adenosine-induced vasodilation ?" Biosignaling in Cardiac and Vascular Systems. Eds.Fujiwara et al., Pergamon Press, Oxford. 292-295 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Tanioka, A., Matsugi, T. & Takase, H.: "Indication of possible association of decrease" Biosignaling in Cardiac and Vascular Systems.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki, H., Tanioka, A. & Ueda, H.: "Possible mechanisms of age-associated changes in vascular function." Biosignaling in cardiac and Vascular Systems Eds.Fujiwara et al., Pergamon Press, Oxford. 284-287 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Moritoki,H.,Tanioka,A.,Maeshiba,Y.,Iwamoto,T.,Ishida,Y.&Araki,H.: "Ageーassociated decrease in histamineーinduced vasodilatation may be due to reduction of cyclic GMP formation." Brit.J.Pharmacol.95. 1015-1022 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,Matsugi,T.,Takase,H.,Ueda,H.&Tanioka,A.: "Evidence for the involvement of cyclic GMP in adenosineーinduced ageーdependent vasodilataion." Brit.J.Pharmacol..,.

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,Yoshikawa,T.,Hisayama,T.&Takase,H.: "Contribution of the endothelial function to vasodilator effect of atrial natriuretic peptide"

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,Tanioka,A.Ueda,H & Matsugi,T.: "Adenosine-induced vasodilation is mediated by cGMP.in:Bioinformatics" Eds.Hatase & Wong,Elsevier,Amsterdam, 251-254 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,Tanioka,A.& Ueda,H.: "Does cGMP mediated adenosine-induced vasodilation?in:Biosignaling in Cardiac and Vascular Systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 292-295 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H,.Tanioka,A.,Matsugi,T.&Takase,H.: "Indication of possible association of decrease in cGMP-mediated vaso-dilation with increase in c GMP-phosphodiesterase activity during aging.:in Biosignaling in Cardiac and Vascular Systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 288-291 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,Tanioka,A.& Ueda,H.: "Possible mechanisms of age-associated changes in vascular function.in:Biosignaling in Cardiac and Vascular Systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 284-287 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Moritoki,H.,et al.: British J.Pharmacology. 95. 1015-1022 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Moritoki,H.et al.: "Possible mechsanisms of age-associated changes in vascular function in:Biosignaling in Cardiac and Vascular Systems," Pergamon Press,

    • Related Report
      1988 Annual Research Report
  • [Publications] Moritoki,H.,et al.: "Does cGMP mediate adenosine-induced vasodilation? in:Biosignaling in Cardiac and Vascular Systems," Pergamon Press,

    • Related Report
      1988 Annual Research Report
  • [Publications] Moritoki,H.,et al.: "Induction of possible association of decrease in cGMP-mediated vasodilation with increase in cGMP-phosphodiesterase activity during aging in:Bisignaling in Cardiac and Vascular Sy" Pergamon Press,

    • Related Report
      1988 Annual Research Report
  • [Publications] Moritoki,H.et al.: "Adenosine-induced vasodilation is mediated by cGMP in:Ihformation Transduction and Processing in Biological Systems" Elsevier,

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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