Ghasemi M, Sadeghipour H, Shafaroodi H, Nezami B G, Gholipour T, Hajrasouliha A R, Tavakoli S, Nobakht M, Moore K P, Mani A R, Dehpour A R
Department of Pharmacology, School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran.
Br J Pharmacol. 2007 Jul;151(5):591-601. doi: 10.1038/sj.bjp.0707279. Epub 2007 May 8.
Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model.
Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation.
The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB(1) antagonist) or capsazepine (vanilloid VR(1) antagonist), but not AM630 (CB(2) antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups.
Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB(1) and vanilloid VR(1) receptors.
阴茎海绵体舒张由非肾上腺素能非胆碱能（NANC）神经传递释放的一氧化氮（NO）介导，对诱导阴茎勃起至关重要，且会受多种病理生理状况影响。然而，肝硬化对勃起功能的外周影响尚不清楚。本研究旨在探讨胆管性肝硬化对大鼠阴茎海绵体NANC介导舒张的影响以及内源性大麻素和一氧化氮系统在该模型中的可能作用。
通过胆管结扎诱导肝硬化。对照组进行假手术。四周后，将阴茎海绵体条带置于标准器官浴槽中，通过施加电场刺激获得NANC介导的舒张。
肝硬化动物的阴茎海绵体条带中NANC介导的舒张增强。花生四烯乙醇胺增强了两组的舒张。AM251（CB(1)拮抗剂）或辣椒素（香草酸VR(1)拮抗剂）而非AM630（CB(2)拮抗剂）可阻止肝硬化条带舒张增强。非选择性NOS抑制剂L-NAME或选择性神经元NOS抑制剂L-NPA均可抑制两组的舒张，但肝硬化组对这些药物的抑制作用更具抗性。两组组织对硝普钠（NO供体）的舒张反应相似。
肝硬化可能通过NO途径并涉及大麻素CB(1)和香草酸VR(1)受体增强大鼠阴茎海绵体的神经源性舒张。
