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

为了探讨缺血和高血糖对阴茎勃起的影响，我们用双侧髂动脉部分阻断致阴茎缺血和四氧嘧啶致高血糖的家兔阴茎海绵体进行药理学实验，缺血：1）神经源性和NO介导的舒张功能受损，L精氨酸可使其恢复;（2）EPS引起的cGMP生成减少;（3）L-NMA和ADMA含量增加，但SDMA含量不增加;这些结果表明，缺血时神经源性和NO介导的阴茎舒张功能受损与L-NMA和ADMA积累增加和NOS活性降低密切相关，这将导致NO产生/释放加速减少。1）SNP诱导的舒张或神经源性和NO介导的舒张均无显著变化，2）减少由卡巴胆碱或硝普钠刺激的环GMP产生。3)NOS活性和鸟苷酸环化酶活性无明显变化; 4）内源性NOS抑制剂L-NMA和ADMA含量降低，而SDMA含量无明显变化。Hyerplatin似乎在几个不同的水平上影响阴茎海绵体中的NO-cGMP途径。缩写：NOS，一氧化氮合酶; L-NMA，N^G甲基-L-精氨酸; ADMA，不对称N^G，N^G-二甲基L-精氨酸; SDMA，对称N^G，N '^G-二甲基L-精氨酸; SNP，硝普钠; EFS，电场刺激

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