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Role of endogenous nitric oxide synthase inhibitors in penile erection and their potential use in the treatment of erectile dysfunction.

Research Project

Project/Area Number 11671538
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionDokkyo University School of Medicine (2000-2001)
Tokyo Medical and Dental University (1999)

Principal Investigator

TSUJII Toshihiko  Dokkyo University School of Medicine, Department of Urology, Associate Professor, 医学部, 助教授 (90217307)

Co-Investigator(Kenkyū-buntansha) AZUMA Hiroshi  Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University Department of Molecular Design, Associate Professor, 生体工学研究所・分子設計部門, 助教授 (20134736)
影山 幸雄  東京医科歯科大学, 医学部, 助手 (10211153)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordspenile erection / corpus cavernosum / nitric oxide svnthase / cyclic GMP / nitric oxide / ischemia / hyperglylcemia / endogenous NOS inhibitors / 勃起障害 / nitric oxide / NOS / guanylate cyclase / 陰茎海面体 / erectile dysfunction(ED) / 一酸化窒素(NO) / 一酸化窒素合成酵素(NOS)
Research Abstract

In order to examine the effect of ischemia and hyperglycemia on the penile erection, we did pharmacological experiments using corpus cavernosum from 1) rabbits with penile ischemia by partial occlusion of bilateral iliac arteries and 2) rabbits with alloxane-induced hyperglycemia.
Ischemia : 1) impaired neurogenic and NO-mediated relaxation that was restored by L arginine; no changes in SNP-induced relaxation, 2) impaired cyclic GMP production induced by EPS, 3) increased tissue contents of L-NMA and ADMA, but not SDMA, 4) reduced NOS activity that was restored by L-arginine. These results suggest that the impaired neurogenic and NO-mediated penile relaxation with ischemia is closely related to the increased accumulation of L-NMA and ADMA and decreased NOS activity, which would result in an accelerated reduction in NO production/release.
Hyoerglycemia : 1) no significant changes in either SNP-induced relaxation or neurogenic and NO-mediated relaxation, 2) reduced cyclic GMP production stimulated by carbachol or sodium niroprusside. 3) no changes in NOS activity and guanylate cyclase, 4) reduced tissue contents of the endogenous NOS inhibitors, L-NMA and ADMA, but not SDMA. Hyerglycemia seems to affect the NO-cGMP pathway in corpus cavernosum at several different levels.
Abbreviations : NOS, nitric oxide synthase ; L-NMA, N^G methyl-L-arginine ; ADMA, asymmetric N^G, N^G-dimethyl L-arginine ; SDMA, symmetric N^G,N'^G-dimethyl L-arginine ; SNP, sodium nitroprusside ; EFS, electrical field stimulation

Report

(3 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Tsujii T, Masuda H, Ichiyanagi N, Goto M Azuma H: "Impaired cGMP production in corpus cavernosum of hyperglycemic rabbits and its reversal by aldose reductase inhibitor"Jpn.J.Pharmacol.. 85(Sppl). 214 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda H, Tsujii T, Okuno T, Kihara K, Goto M Azuma H: "Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity in the impaired neurogenic relaxationof the rabbit proximal urethra with ischaemia"Br.J.Pharmacol.,. 133. 97-106 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda H, Tsujii T, Azuma H, Oshima H.: "Role of a central muscarinic cholinergic pathway for relaxation of the proximal urethra during voiding phase in the rats"J Urol.. 165. 999-1003 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichiyanagi N, Tsu.jii T, Masuda K.Goto M.Azuma H: "Changed responsiveness of the detrusor in rabbits with ailoxan-induced hyperglycemia : possible role of 5-hydroxytriptamine for diabetic bladder dysfunction"J Urol.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsujii T, Masuda H, Ichiyanagi N, Goto M and Azuma H.: "Impaired cGMP production in corpus cavernosum of hyperglycemic rabbits and its reversal by aldose reductase inhibitor"Jpn. J. Pharmacol.. 85(Sup1). 214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda H, Tsujii T, Okuno T, Kihara K, Goto M and Azuma H: "Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity in the impaired neurogenic relaxation of the rabbit proximal urethra with Ischemia"Br. J. Pharmacol.. 133. 97-106 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary

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

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