Effect of nitric oxide synthase inhibitor Nω-Nitro-L-arginine on the penile erectile function of healthy male rats / 中国医师杂志

ABSTRACT

Ojective To investigate the direct effect of exogenous NOS inhibitor Nω-Nitro-L-arginine (L-NNA) on the erectile function of healthy male rats in order to clarify the mechanism of the erectile dysfunction of type 2 diabetic rats.Methods L-NNA (50 mg/kg) was administered by oral gavage to Sprague Dawley (SD) rats for 16 weeks to induce rat model of NOS inhibition.By the end of the experiment,corpora cavernosa was isolated from the rats under anesthetization and fixed in an organ chamber for the examination of relaxation function response to acetylcholine (ACh) to reflect erectile function.Enzymelinked immunosorbent assay (ELISA) was performed to determine the content of cyclic guanosine monophosphate (cGMP) in cavernosal tissue.NOS activity and nitric oxide (NO) content were measured by colorimetric method.Western blotting was employed to detect the protein expression of NOS and phosphodiesterase 5 (PDE5).The activity of the antioxidative enzyme superoxide dismutase (SOD) and content of the lipid peroxidative product malondialdehyde (MDA) were analyzed to reflect oxidative stress.Results In comparison with control group,the relaxation response to acetylcholine of corpus cavernosum was significantly impaired in L-NNA model rats,indicating penile erectile dysfunction.Either decreased contents of NO and cGMP or suppressed activity of NOS were observed in the corpus cavernosum of L-NNA model rats and in accompany with the down-regulation of endothelial NOS (eNOS) and neuronal NOS (nNOS) expression,up-regulation of inducible NOS (iNOS) and PDE5 expression as well as an increase of oxidative stress.Incubation of corpus cavernosum from control rats with L-NNA (1-10 μmol/L) ex vivo for 30 min could also inhibit the relaxation function responses to acetylcholine in a dose-dependent manner.Treatment with L-arginine ex vivo for 45 min could improve the impairments of relaxation function responses to acetylcholine of corpus cavernosum induced by L-NNA in vivo and ex vivo.Conclusions Exogenous NOS inhibitor L-NNA could induce penile erectile dysfunction in healthy male rats and the mechanism may be related to reducing NO content and increasing oxidative stress.