The effects of combined free radical scavenger and sildenafil therapy on age-associated erectile dysfunction: An animal model

Introduction: Aging results in erectile dysfunction that is partially attributed to decreased nitric oxide (NO) and increased free radical generation. Vitamin E enhances endothelial cell function and acts as a free radical scavenger; however, its benefits on erectile function in the elderly are unknown. Aims: The aim of the following study is to determine if Vitamin E alone, or in combination with the phosphodiesterase 5 inhibitor sildenafil, may improve erectile function and the NO signaling in a cohort of aged (13-15 month old) rats. Materials and Methods: Male Sprague-Dawley rats (n = 28) were divided based upon age into young (4-5 months old, n = 7) and aged (13-15 months old, n = 21) cohorts. Aged rats were treated with Vitamin E, sildenafil or a combination of both. Penile cavernosal and dorsal nerve tissues were evaluated for neuronal nitric oxide synthase (nNOS) and caveolin-1 expression. Erectile function was assessed through intra-cavernous pressure (ICP) recordings. Results: nNOS and cavoelin-1 were significantly decreased in aged rats compared with young controls. In aged rats, both Vitamin E and sildenafil partially recovered nNOS expression but when combined, a synergistic elevation in nNOS was observed. The significant decreases in ICP recorded in aged rats were improved with sildenafil; however, Vitamin E did not yield any additional improvements in ICP. Conclusions: Diminished levels of nNOS and caveolin-1 are found in aged rats. When combined with sildenafil, Vitamin E synergistically increased nNOS expression. Since biochemical gains were not realized physiologically, other contributing factors likely exist.