Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
J Sex Med. 2013 Mar;10(3):704-18. doi: 10.1111/j.1743-6109.2012.02912.x. Epub 2012 Sep 18.
Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs.
The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions.
Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat.
Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated.
The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response.
These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED.
可溶性鸟苷酸环化酶（sGC）是一氧化氮（NO）的受体，在 NO 形成或生物利用度受损的病理生理条件下，会发生勃起功能障碍（ED）。
本研究旨在探讨 sGC 刺激剂 BAY 41-8543 在生理和病理生理条件下对勃起反应的影响。
在麻醉大鼠中，研究了腔内（ic）注射 BAY 41-8543 对海绵体内压（ICP）的增加。
研究了 ic 注射 BAY 41-8543 引起的 ICP/MAP 的增加以及 BAY 41-8543 与外源性和内源性释放的 NO 的相互作用，并评估了 sGC 刺激剂对海绵体神经损伤的影响。研究了 ic 注射乙酰胆碱引起 ICP/MAP 增加的机制。
ic 注射 BAY 41-8543 增加了 ICP/MAP 和反应持续时间。BAY 41-8543 的效力低于硝普钠（SNP），ic 注射 BAY 41-8543 和 SNP 产生的反应大于单独使用任何一种药物的反应之和。同时 ic 注射 BAY 41-8543 和海绵体神经刺激产生的反应大于任何一种干预措施单独产生的反应。阿托品和海绵体神经挤压损伤降低了对神经刺激的反应，而 ic 注射 BAY 41-8543 恢复了反应。
这些数据表明 BAY 41-8543 具有显著的勃起活性，并且可以与外源性和内源性释放的 NO 协同作用。本研究表明，阿托品和神经挤压损伤可减弱对海绵体神经刺激的反应，而 BAY 41-8543 可恢复反应。阿托品、L-NAME 和六烃季铵的结果表明，ic 注射乙酰胆碱的反应是由毒蕈碱受体介导的，NO 的释放没有烟碱受体的显著作用。这些结果表明 BAY 41-8543 将在 ED 的治疗中有用。
