Ignarro L J, Bush P A, Buga G M, Wood K S, Fukuto J M, Rajfer J
Department of Pharmacology, University of California, Los Angeles 90024.
Biochem Biophys Res Commun. 1990 Jul 31;170(2):843-50. doi: 10.1016/0006-291x(90)92168-y.
In the presence of functional adrenergic and cholinergic blockade, electrical field stimulation relaxes corpus cavernosum smooth muscle by unknown mechanisms. We report here that electrical field stimulation of isolated strips of rabbit corpus cavernosum promotes the endogenous formation and release of nitric oxide (NO), nitrite, and cyclic GMP. Corporal smooth muscle relaxation in response to electrical field stimulation, in the presence of guanethidine and atropine, was abolished by tetrodotoxin and potassium-induced depolarization, and was markedly inhibited by NG-nitro-L-arginine, NG-amino-L-arginine, oxyhemoglobin, and methylene blue, but was unaffected by indomethacin. The inhibitory effects of NG-substituted analogs of L-arginine were nearly completely reversed by addition of excess L-arginine but not D-arginine. Corporal smooth muscle relaxation elicited by electrical field stimulation was accompanied by rapid and marked increases in tissue levels of nitrite and cyclic GMP, and all responses were nearly abolished by NG-nitro-L-arginine. These observations indicate that penile erection may be mediated by NO generated in response to nonadrenergic-noncholinergic neurotransmission.
在存在功能性肾上腺素能和胆碱能阻滞的情况下,电场刺激通过未知机制使海绵体平滑肌松弛。我们在此报告,对兔海绵体离体条带进行电场刺激可促进一氧化氮(NO)、亚硝酸盐和环磷酸鸟苷(cGMP)的内源性生成和释放。在胍乙啶和阿托品存在的情况下,电场刺激引起的海绵体平滑肌松弛被河豚毒素和钾诱导的去极化所消除,并被NG-硝基-L-精氨酸、NG-氨基-L-精氨酸、氧合血红蛋白和亚甲蓝显著抑制,但不受吲哚美辛影响。添加过量的L-精氨酸可几乎完全逆转L-精氨酸的NG取代类似物的抑制作用,而D-精氨酸则不能。电场刺激引起的海绵体平滑肌松弛伴随着组织中亚硝酸盐和环磷酸鸟苷水平的快速显著升高,并且所有反应几乎都被NG-硝基-L-精氨酸消除。这些观察结果表明,阴茎勃起可能由非肾上腺素能-非胆碱能神经传递产生的NO介导。