Title

Gene transfer of extracellular SOD to the penis reduces O-2(-.) and improves erectile function in aged rats

Authors

Authors

T. J. Bivalacqua; J. S. Armstrong; J. Biggerstaff; A. B. Abdel-Mageed; P. J. Kadowitz; W. J. G. Hellstrom;H. C. Champion

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Am. J. Physiol.-Heart Circul. Physiol.

Keywords

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

Abstract

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.

Journal Title

American Journal of Physiology-Heart and Circulatory Physiology

Volume

284

Issue/Number

4

Publication Date

1-1-2003

Document Type

Article

DOI Link

http://dx.doi.org/10.1152/ajpheart.00770.2002

Language

English

First Page

H1408

Last Page

H1421

WOS Identifier

WOS:000181425900043

ISSN

0363-6135

Recommended Citation

"Gene transfer of extracellular SOD to the penis reduces O-2(-.) and improves erectile function in aged rats" (2003). Faculty Bibliography 2000s. 3629.
https://stars.library.ucf.edu/facultybib2000/3629