Gene transfer of extracellular SOD to the penis reduces O2-· and improves erectile function in aged rats

Trinity J. Bivalacqua, Jeffrey S. Armstrong, John Biggerstaff, Asim B. Abdel-Mageed, Philip J. Kadowitz, Wayne J.G. Hellstrom, Hunter C. Champion

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H1408-H1421
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number4 53-4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Keywords

  • Aging
  • Erectile dysfunction
  • Gene therapy
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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