Tolerance to isosorbide dinitrate in isolated strips of rabbit corpus cavernosum

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 not likely to be the operating mechanism for nitrate tolerance. We suggest that tolerance may result from the impairment of biotransformation of ISDN in rabbit cavernosal smooth muscle.