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1 Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA
2 Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA
3 Biomolecular Research Annex, University of Central Florida, Orlando, FL, USA; Biomolecular Research Annex, University of Central Florida, Orlando, FL, USA
4 Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
5 Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA; Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA
6 Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: hchampi{at}tulane.edu.
Increased superoxide anion may contribute to vascular dysfunction in aging. In aged cavernosal tissue, lucigenin-enhanced chemiluminescence demonstrated a 3-fold increase in superoxide formation, and 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 SOD (EC-SOD) mRNA or protein. In vivo adenoviral 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 (ED) associated with aging is related in part to an increase in cavernosal superoxide anion 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 ED.
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