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.