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.

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.

CONCLUSIONS

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.