The selective Rho-kinase inhibitor azaindole-1 has long-lasting erectile activity in the rat.
The selective Rho-kinase inhibitor azaindole-1 has long-lasting erectile activity in the rat.
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DOI：
10.1016/j.urology.2012.10.039
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发表时间：
2013-02
期刊：
影响因子：
2.1
通讯作者：
Kadowitz PJ
中科院分区：
文献类型：
--
作者：
Lasker GF;Pankey EA;Allain AV;Murthy SN;Stasch JP;Kadowitz PJ
目的：研究选择性Rho激酶（ROCK）抑制剂azaindole-1对生理和病理条件下大鼠勃起功能的影响。海绵体内（i.c.）在对照条件下和当NANC神经传递和胆碱能功能或sGC被抑制时或在海绵体神经挤压损伤后，在麻醉大鼠中研究了注射氮杂吲哚-1对ICP、ICP/MAP、AUC和反应持续时间的变化。i.c.与原型ROCK抑制剂法舒地尔相比，注射氮杂吲哚-1产生ICP/MAP和AUC的剂量相关性增加，其在所研究的最高剂量下持续时间长。勃起反应没有改变7-NI和阿托品的剂量，减少海绵体神经刺激的反应由86%，表明它们是独立的海绵体神经或激活的毒蕈碱受体的海绵体中的NO释放。在减弱对NO供体SNP的反应的剂量下，sGC抑制剂ODQ没有改变对氮杂吲哚-1的勃起反应，这表明它们不依赖于对sGC的作用。海绵体神经挤压损伤后，对IC注射氮杂吲哚-1或Y-27632的勃起反应没有减弱，据报道，这是NO/cGMP依赖性的。目前的研究表明氮杂吲哚-1具有持久的勃起活性，其独立于NO释放、毒蕈碱受体或sGC激活或海绵体神经的完整性。
To investigate the effects of the selective Rho-kinase (ROCK) inhibitor azaindole-1 on erectile function under physiologic and pathophysiologic conditions in the rat. The effect of intracavernosal (i.c.) injections of azaindole-1 on change in ICP, ICP/MAP, AUC, and response duration were investigated in the anesthetized rat under control conditions and when NANC neurotransmission and cholinergic function or sGC were inhibited or after cavernosal nerve crush injury. The i.c. injections of azaindole-1 produced dose-related increases in ICP/MAP and AUC that were long lasting at the highest doses studied when compared with the prototypical ROCK-inhibitor fasudil. Erectile responses were not altered by 7-NI and atropine in doses that reduced the response to cavernosal nerve stimulation by 86%, indicating that they were independent of NO release by cavernosal nerves or activation of muscarinic receptors in the corpora cavernosa. Erectile responses to azaindole-1 were not altered by the sGC inhibitor ODQ in a dose that attenuated responses to the NO donor SNP indicating that they were independent of an action on sGC. The erectile response to ic injections of azaindole-1 or Y-27632 which was reported to be NO/cGMP- dependent were not attenuated after cavernosal nerve crush injury. The present studies indicate azaindole-1 has long lasting erectile activity that is independent of NO release, muscarinic receptor, or sGC activation or the integrity of the cavernosal nerves.
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影响因子：
8.3
作者：
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通讯作者：
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