Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula in penile tissues of aged and diabetic rats

Abstract

We investigated the mechanisms underlying the effects of an herbal formula (HF) in improving erectile dysfunction (ED), particularly in terms of nitric oxide (NO)-cGMP pathways. Two different rat models, 24-month-old rats (aging) and 10-month-old rats maintained chronically high plasma glucose levels (328 +/- 89 mg/dL) diabetes mellitus (DM), were treated with HF (100 mg/kg per day) for 10 days. We examined the electrostimulated penile responses, expression and activity of three enzymes: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS) and caveolin-1 (CaV-1), and cGMP concentration that act upon the major NO-cGMP signaling pathways in penile tissue. Effect of HF on cGMP degradation was also examined using bovine vascular smooth-muscle cells pretreated with an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In aging and DM rats, the severely reduced peak intracavernous pressures (ICPs) in penile tissues were restored completely after HF treatment, and HF treatment significantly made the latency period earlier. Furthermore, the penile expression levels of nNOS, eNOS and CaV-1, Ca2+ -dependent NOS activities and cGMP concentrations were increased significantly in the HF-treated rats. Particularly, inhibitory effect of HF on cGMP degradation was confirmed also in cell system. These results indicate that new HF originated from a Korean traditional medicine (Ojayounjonghwon described in 'Dong Ui Bo Gam') can ameliorate the ED impaired by peripheral neuropathy and/or angiopathy, via the activation of NO-cGMP pathways.