Tehran University Medical Journal

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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.

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Background: Relaxation of the corpus cavernosum plays an important role in penile erection. Previous studies have suggested that nitric oxide (NO) appears to be the most important relaxant involved in the erection process. The aim of the present study was to evaluate the effect of cholestasis in nNOS and eNOS activity of corpus cavernosum.
Methods: forty-two adult male Sprague-Dawley rats were divided equally into seven groups: control, sham operated, 2-, 7-, and 14-day bile duct-ligated animals, 7-day bile duct-ligated chronically treated with L-NAME (3mg/kg/day, i.p.) and 7-day bile duct-ligated animals chronically treated with Naltrexone (20 mg/kg/day, i.p.). The animals in each group were killed and the cavernosal tissues analyzed histologically by light and transmission electron microscopy, with NOS activity detected on NANC nerves and endothelium using an NADPH-diaphorase staining technique.
Results: our results showed that NADPH diaphorase staining in corporal NANC nerves and endothelium of sham-operated and control group had equal intensity. The staining was more intense in 2-day cholestatic rats than in control group, the staining intensity increased in 7-, and 14-day groups too. There were no significant differences between control group and 7-day cholestatic rats that had been treated chronically with L-NAME or Naltrexone.
Conclusions: These results state that in corpus cavernosum of cholestatic rats there is a time-dependent increase in NOS activity of the corporal NANC nerves and endothelium. inhibition of nitric oxide and endogenous opioids by L-NAME or Naltrexone during cholestasis may play a key role in preventing the adverse effects of cholestasis.

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Background: It is well known that erectile dysfunction is most commonly associated with diabetes, affecting 35% to 75% of men with diabetes mellitus. Several studies have been carried out to find appropriate strategies for treatment of diabetes-induced erectile dysfunction. The aim of the present study was to investigate the ability of acute administration of the endogenous cannabinoid anandamide in vitro to alter the NANC-mediated relaxation of corpus cavernosum from diabetic rats and the possible role of nitric oxide in this manner.

Methods: Diabetes was induced by the administration of streptozotocin for eight weeks. Corpora cavernosa were isolated in organ baths for measurement of agonist-evoked or electrical field stimulation (EFS)-evoked smooth muscle tensions.

Results: The neurogenic relaxation of phenylephrine (7.5 µM) precontracted isolated corporal strips was impaired in diabetic animals. Anandamide (0.3, 1 and 3 µM) enhanced the relaxant responses to EFS in diabetic strips in a dose-dependent manner. This effect was antagonized by either the selective cannabinoid CB1 receptor antagonist AM251 (1 µM) or the selective vanilloid receptor antagonist capsazepine (3 µM). Concurrent administration of partially effective doses of L-arginine (10 µM) and anandamide (0.3 µM) exerted a synergistic improvement in EFS-induced relaxation of diabetic strips (p<0.001). The relaxant responses to the nitric oxide donor sodium nitroprusside of the subjects in the diabetic and control groups were similar.

Conclusion: For the first time, we demonstrated that acute administration of an endogenous cannabinoid, alone or in combination with L-arginine could improve the NO-mediated relaxation of cavernosal smooth muscle in diabetic rats and this effect was mediated by cannabinoid CB1 and vanilloid VR1 receptors within the tissue.