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

Objective To investigate the effects of the long-term oral administration o f L-arginine on the impaired neurogenic and endothelium-dependent relaxatio n responses of corpus cavernosum smooth muscle from alloxan-induced diabeti c rabbits. Materials and methods Thirty-two New Zealand white rabbits were used in fou r 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 inductio n of diabetes; in group 3, 6 U/day of insulin was injected subcutaneously; group 4 was maintained with no treatment (as littermate controls) for 8 wee ks. Thereafter, the rabbits were killed by exsanguination and the penis rem oved 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 e lectrical field stimulation and carbachol from rabbits in group 1 were less than in controls; the responses to carbachol were not significantly impair ed 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 relax ation by diabetes appears to involve an alteration in nitric oxide/cyclic G MP pathway. Administration of oral L-arginine increased endothelium-depende nt relaxation, probably through activating nitric oxide synthase. Additiona lly, decreasing elevated blood glucose concentration and advanced glycosyla tion products by insulin treatment protected endothelium-dependent relaxati on, whereas neither L-arginine nor insulin treatment restored impaired neur ogenic relaxation.