Gene transfer of extracellular SOD to the penis reduces O-2(-.) and improves erectile function in aged rats
Abbreviated Journal Title
Am. J. Physiol.-Heart Circul. Physiol.
gene therapy; aging; nitric oxide; erectile dysfunction; NITRIC-OXIDE SYNTHASE; SUPEROXIDE-DISMUTASE; ENDOTHELIAL DYSFUNCTION; SMOOTH-MUSCLE; OXIDATIVE STRESS; ANGIOTENSIN-II; CORPUS CAVERNOSUM; RELAXATION; EXPRESSION; HYPERTENSION; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease
Increased superoxide anion (O-2(-.)) may contribute to vascular dysfunction in aging. In aged cavernosal tissue, lucigenin-enhanced chemiluminescence demonstrated a threefold increase in superoxide formation, and the oxidative fluorescent probe hydroethidine indicated higher superoxide levels throughout the aged penis. This increase in superoxide was associated with impaired cavernosal nerve-mediated and agonist-induced erectile responses, increased nitrotyrosine staining, and lower cGMP levels, but no compensatory change in cavernosal extracellular (EC)-superoxide dismutase (EC-SOD) mRNA or protein. In vivo adenoviral (Ad) gene transfer of EC-SOD to the penis resulted in higher expression of EC-SOD mRNA, protein, SOD activity, cGMP levels, and lower nitrotyrosine staining. Transfection with AdCMVEC-SOD resulted in a significant increase in erectile response to cavernosal nerve stimulation, ACh, and zaprinast to a magnitude similar to young rats. These data provide evidence in support of the hypothesis that erectile dysfunction associated with aging is related in part to an increase in cavernosal O-2 formation. Gene-transfer of EC-SOD reduces superoxide formation and restores age-associated erectile function and may represent a novel therapeutic target for the treatment of erectile dysfunction.
American Journal of Physiology-Heart and Circulatory Physiology
"Gene transfer of extracellular SOD to the penis reduces O-2(-.) and improves erectile function in aged rats" (2003). Faculty Bibliography 2000s. 3629.