Corporal reactivity to adenosine and prostaglandin E1 in alloxan-induced diabetic rabbit corpus cavernosum, and the effect of insulin therapy.

OBJECTIVE: To investigate the changes in corporal reactivity to adenosine and prostaglandin E1 (PGE1 ) in corpus cavernosal strips from alloxan-induced diabetic rabbits and to determine the effects of insulin therapy. MATERIALS AND METHODS: Twenty-four New Zealand white rabbits were studied in three equal groups: group 1, control; group 2, diabetes induced by the administration of alloxan hydrochloride intravenously; group 3, as group 2 but with insulin administered after the induction of diabetes. At the end of 8 weeks, the reactivity of corpus cavernosal strips from the animals was assessed in organ chambers. RESULTS: The relaxation responses of corpus cavernosal strips to adenosine were similar in all groups, but the response to PGE1 was impaired in groups 2 and 3 compared with that in controls. CONCLUSION: If vasoactive drugs are to be used for the diagnosis or treatment of diabetic erectile impotence, direct-acting vasodilators, e.g. adenosine, must be used. In alloxan-induced diabetes, the corporal reactivity to PGE1 was impaired and insulin therapy did not restore the relaxation responses.

The effects of long-term oral administration of L-arginine on the erectile response of rabbits with alloxan-induced diabetes.

OBJECTIVE: To investigate the effects of the long-term oral administration of L-arginine on the impaired neurogenic and endothelium-dependent relaxation responses of corpus cavernosum smooth muscle from alloxan-induced diabetic rabbits. MATERIALS AND METHODS: Thirty-two New Zealand white rabbits were used in four groups of eight each. In group 1, the rabbits received no treatment after the induction of diabetes with alloxan hydrochloride given intravenously; in group 2, L-arginine (1 mg/mL) was administered orally after the induction of diabetes; in group 3, 6 U/day of insulin was injected subcutaneously; group 4 was maintained with no treatment (as litter-mate controls) for 8 weeks. Thereafter, the rabbits were killed by exsanguination and the penis removed en bloc. The reactivity of corpus cavernosum strips from the penis was then assessed in organ chambers. RESULTS: Relaxation and contraction responses of corpus cavernosum strips to sodium nitroprusside and potassium chloride, respectively, were similar in all groups. Relaxation responses of corpus cavernosum strips elicited by electrical field stimulation and carbachol from rabbits in group 1 were less than in controls; the responses to carbachol were not significantly impaired in group 2 and 3, whereas responses to electrical field stimulation were impaired in both groups when compared with the control group. CONCLUSION: The impairment of endothelium-dependent and nerve-mediated relaxation by diabetes appears to involve an alteration in nitric oxide/cyclic GMP pathway. Administration of oral L-arginine increased endothelium-dependent relaxation, probably through activating nitric oxide synthase. Additionally, decreasing elevated blood glucose concentration and advanced glycosylation products by insulin treatment protected endothelium-dependent relaxation, whereas neither L-arginine nor insulin treatment restored impaired neurogenic relaxation.

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.