Gene Transfer Of Extracellular Sod To The Penis Reduces O2-· And Improves Erectile Function In Aged Rats
Aging; Erectile dysfunction; Gene therapy; Nitric oxide
Increased superoxide anion (O2-·) 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 O2-· 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
Source API URL
Bivalacqua, Trinity J.; Armstrong, Jeffrey S.; and Biggerstaff, John, "Gene Transfer Of Extracellular Sod To The Penis Reduces O2-· And Improves Erectile Function In Aged Rats" (2003). Scopus Export 2000s. 1811.