Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase
Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase
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DOI：
10.1002/j.1939-4640.2002.tb02601.x
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发表时间：
2002-01-01
影响因子：
--
通讯作者：
Sezen, SF
中科院分区：
文献类型：
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作者：
Burnett, AL;Chang, AG;Sezen, SF
随着人们对一氧化氮(NO)介导阴茎勃起的认识，内皮型一氧化氮合酶(ENOS)已被认为参与了这一功能。我们开展了这项研究，应用eNOS基因定向缺失的转基因小鼠(eNOS-/-小鼠)作为一种实验方法，评估eNOS在体内胆碱刺激的勃起功能中的重要性。对eNOS-/-小鼠和野生型对照组进行药物刺激联合阴茎海绵体内注射卡巴胆碱(3 Ng)和次最大海绵体神经(CN)电刺激(16 Hz，5毫秒，1V)，同时监测阴茎海绵体内压(ICP)，并进行一氧化氮合酶(NO)活性的生化测定和eNOS蛋白含量的Western印迹分析。联合海绵体内注射卡巴胆碱和次极量CN电刺激可增加野生型小鼠由CN电刺激引起的记录的颅内压(从35.7+/-2.7至48.1+/-5.5 mm Hg，P<；0.05)，但对eNOS-/-小鼠无显著影响(从54.9+/-6.3至51.0+/-9.5 mm Hg，无显著意义[NS])。预先给予非选择性一氧化氮合酶抑制剂-L-精氨酸甲酯(L-NAME，海绵体内100 mg)可阻断eNOS-/-小鼠电刺激的颅内压反应至基线水平(37.8+/-4.4vs12.7+/-4.0 mm Hg，P<；0.05)。在eNOS-/-小鼠的阴茎中，约60%的野生型阴茎水平的NO合成酶活性被保留(NS)，eNOS蛋白缺失。我们的结论是，eNOS-/-小鼠维持勃起功能的基础是一种非胆碱能但不依赖的机制，eNOS生理上介导了胆碱能刺激下的阴茎勃起。
With the current understanding that nitric oxide (NO) mediates penile erection, the endothelial isoform of NO synthase (eNOS) has been implicated in this function. We undertook this study applying transgenic mice with targeted deletion of the eNOS gene (eNOS-/- mice) as an experimental approach to evaluate the importance of eNOS in cholinergically stimulated erectile function in vivo. Combined pharmacostimulation with intracavernosal carbachol (3 ng) administration and submaximal cavernous nerve (CN) electrical stimulation (16 Hz, 5 millisecond, 1 V) simultaneous with intracavernosal pressure (ICP) monitoring, and both biochemical assay of NO synthase activity and Western blot analysis of eNOS protein content in penile tissue, were performed on eNOS-/- mice and wild-type controls. Combined intracavernosal carbachol administration and submaximal CN electrical stimulation raised the recorded ICP, elicited by CN electrical stimulation alone in wild-type mice (from 35.7 +/- 2.7 to 48.1 +/- 5.5 mm Hg, P < .05) but not in eNOS-/- mice (from 54.9 +/- 6.3 to 51.0 +/- 9.5 mm Hg, not significant [NS]). Pretreatment with the nonselective nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 100 mg intracavernosally) blocked electrically stimulated ICP responses in eNOS-/- mice to baseline levels (37.8 +/- 4.4 vs 12.7 +/- 4.0 mm Hg, P < .05). In penes of eNOS-/- mice, approximately 60% NO synthase activity of wildtype penis levels was retained (NS), and eNOS protein was absent. We concluded that eNOS-/- mice preserve erectile function on the basis of a noncholinergic but NO-dependent mechanism and that eNOS physiologically mediates penile erection under cholinergic stimulation.