Tolerance to isosorbide dinitrate in isolated strips of rabbit corpus cavernosum

The aim of this study was to investigate whether prolonged exposure to a hi gh concentration of isosorbide dinitrate (ISDN) would result in tolerance b eing developed against its relaxant activity in strips of corpus cavernosum , pre-contracted by phenylephrine. Under these conditions, relaxation induc ed by ISDN was found. to be significantly reduced. Strips made tolerant to ISDN remained fully responsive to sodium nitroprusside and papaverine. Elec trical field stimulation evoked relaxations which were persistent in the pr esence of tolerance-inducing conditions. These results indicate that desens itization 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 mu scle.