Tolerance to isosorbide dinitrate in isolated strips of rabbit corpus cavernosum

Uma S., Yildirim Ş. , Sarioglu Y., Butuner C., Yildirim K.

INTERNATIONAL JOURNAL OF ANDROLOGY, vol.21, no.6, pp.364-369, 1998 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 6
  • Publication Date: 1998
  • Doi Number: 10.1046/j.1365-2605.1998.00140.x
  • Page Numbers: pp.364-369


The aim of this study was to investigate whether prolonged exposure to a high concentration of isosorbide dinitrate (ISDN) would result in tolerance being developed against its relaxant activity in strips of corpus cavernosum, pre-contracted by phenylephrine. Under these conditions, relaxation induced by ISDN was found. to be significantly reduced. Strips made tolerant to ISDN remained fully responsive to sodium nitroprusside and papaverine. Electrical field stimulation evoked relaxations which were persistent in the presence of tolerance-inducing conditions. These results indicate that desensitization of guanylate cyclase activity is trot likely to be the operating mechanism for nitrate tolerance. We suggest that tolerance may result from the impairment of biotransformation of ISDN ill rabbit cavernosal smooth muscle.