Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.
Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.
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DOI：
10.1097/00006254-199205000-00026
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发表时间：
1992-05
期刊：
影响因子：
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通讯作者：
J. Rajfer;W. Aronson;P. A. Bush;F. Dorey;L. Ignarro
中科院分区：
文献类型：
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作者：
J. Rajfer;W. Aronson;P. A. Bush;F. Dorey;L. Ignarro
背景一氧化氮是血管内皮细胞衍生的松弛因子。我们试图确定它是否与阴茎勃起的阴茎海绵体松弛有关。众所周知，这种平滑肌的松弛发生在非肾上腺素能、非胆碱能神经元的刺激下。方法对21例阳萎患者阴茎海绵体组织切片进行研究。固定的平滑肌标本用胍乙啶和阿托品进行预处理，然后用苯肾上腺素进行亚极收缩。然后，我们研究了对电场刺激和一氧化氮刺激的平滑肌松弛反应。结果电场刺激使海绵体产生明显的、短暂的、频率依赖性的松弛，在N-硝基-L精氨酸和N-氨基-L-精氨酸存在下被抑制，选择性地抑制L-精氨酸生物合成一氧化氮。过量的L-精氨酸的加入，而不是D-精氨酸的加入，在很大程度上逆转了这些抑制作用。一氧化氮的特异性释放(由S-亚硝基-N-乙酰青霉胺)引起海绵体快速、完全和浓度依赖性的松弛。环鸟苷(GMP)磷酸二酯酶的选择性抑制剂(M&B 22,948)可增强电刺激或一氧化氮引起的松弛。亚甲基蓝抑制细胞的松弛，抑制环状GMP的合成。结论我们的研究结果支持一氧化氮参与非肾上腺素、非胆碱能神经传递的假说，非肾上腺素能、非胆碱能神经传递导致阴茎勃起的阴茎海绵体平滑肌松弛。这一途径的缺陷可能会导致某些形式的阳萎。
BACKGROUND Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. METHODS We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. RESULTS Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis. CONCLUSIONS Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.