Role of endogenous nitric oxide synthase inhibitors in penile erection and their potential use in the treatment of erectile dysfunction.

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In order to examine the effect of ischemia and hyperglycemia on the penile erection, we did pharmacological experiments using corpus cavernosum from 1) rabbits with penile ischemia by partial occlusion of bilateral iliac arteries and 2) rabbits with alloxane-induced hyperglycemia.Ischemia : 1) impaired neurogenic and NO-mediated relaxation that was restored by L arginine; no changes in SNP-induced relaxation, 2) impaired cyclic GMP production induced by EPS, 3) increased tissue contents of L-NMA and ADMA, but not SDMA, 4) reduced NOS activity that was restored by L-arginine. These results suggest that the impaired neurogenic and NO-mediated penile relaxation with ischemia is closely related to the increased accumulation of L-NMA and ADMA and decreased NOS activity, which would result in an accelerated reduction in NO production/release.Hyoerglycemia : 1) no significant changes in either SNP-induced relaxation or neurogenic and NO-mediated relaxation, 2) reduced cyclic GMP production stimulated by carbachol or sodium niroprusside. 3) no changes in NOS activity and guanylate cyclase, 4) reduced tissue contents of the endogenous NOS inhibitors, L-NMA and ADMA, but not SDMA. Hyerglycemia seems to affect the NO-cGMP pathway in corpus cavernosum at several different levels.Abbreviations : NOS, nitric oxide synthase ; L-NMA, N^G methyl-L-arginine ; ADMA, asymmetric N^G, N^G-dimethyl L-arginine ; SDMA, symmetric N^G,N'^G-dimethyl L-arginine ; SNP, sodium nitroprusside ; EFS, electrical field stimulation