Tehran University Medical Journal (Jun 2008)
Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system
Abstract
Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO) is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC) nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC)-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM) and atropine (1 µM) to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM) and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz) to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM), as an NO donor, were assessed. Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01). Anandamide potentiated the relaxations in both groups (P<0.05). The cannabinoid CB1 receptor antagonist AM251 (10 µM) and the vanilloid receptor antagonist capsazepine (10 µM) each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01). The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM) inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM) was similar in the two groups.Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and cannabinoid CB1 and vanilloid VR1 receptors.
