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

    Authors

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

    Comments

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    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

    Language

    English

    First Page

    H1408

    Last Page

    H1421

    WOS Identifier

    WOS:000181425900043

    ISSN

    0363-6135

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