HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Magee, T. R. Articles by Gonzalez-Cadavid, N. F. Search for Related Content PubMed PubMed Citation Articles by Magee, T. R. Articles by Gonzalez-Cadavid, N. F. Agricola Articles by Magee, T. R. Articles by Gonzalez-Cadavid, N. F.

Gene Therapy of Erectile Dysfunction in the Rat with Penile Neuronal Nitric Oxide Synthase¹

^a Departments of Urology ^b Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90509 ^c Research and Education Institute, Harbor-UCLA Medical Center, Torrance, California 90502

Gene transfer to the penile corpora cavernosa of constructs of the inducible and endothelial nitric oxide synthase (NOS) cDNAs ameliorates erectile dysfunction in aged rats. In this study, we investigated whether the neuronal NOS (nNOS) variant responsible for erection, penile nNOS (PnNOS), can exert a similar effect, and whether the combination of electroporation with a helper-dependent adenovirus (AdV) improves gene transfer. PnNOS and ß-galactosidase cDNAs were cloned in plasmid (pCMV-PnNOS; pCMV-ß-gal) and "gutless" AdV (AdV-CMV-PnNOS; AdV-CMV-ß-gal) vectors, and injected into the penis of adult (ß-gal) or aged (PnNOS) rats, with or without electroporation. Penile erection was measured at different times after PnNOS cDNA injection, by electrical field stimulation of the cavernosal nerve. The expression of ß-galactosidase or PnNOS was estimated in penile tissue by either histochemistry and luminometry or Western blot, and the effects of AdV-CMV-PnNOS on mRNA expression were examined by a DNA microarray. We found that electroporation increased pCMV-ß-gal uptake, and its expression was detectable at 56 days. In the aged rats treated with pCMV-PnNOS and electroporation, the maximal intracavernosal:mean arterial pressure ratios were elevated for 11 and 18 days when compared with those in controls. Electroporation intensified penile uptake of as few as 10⁶ viral particles (vp) of AdV-CMV-ß-gal, and with 10⁷ vp ß-galactosidase was still detectable at 60 days. Electroporated AdV-CMV-PnNOS (10⁷ vp) was effective at 18 days in stimulating the erection of aged rats, without inducing the expression of cytotoxic genes. In conclusion, intracavernosal gene therapy with PnNOS cDNA corrected the aging-related erectile dysfunction for at least 18 days when given by electroporation in a helper-dependent AdV at low viral loads.

First decision: 14 November 2001.

¹ The experimental studies conducted by our group were funded by NIH grant R01DK-53069 and in part by grant G12RR-03026.

² Correspondence: Nestor F. Gonzalez-Cadavid, Harbor-UCLA Research and Education Institute, Urology, Bldg. F-6, 1124 West Carson St., Torrance, CA 90502. FAX: 310 222 1914; ncadavid{at}ucla.edu

This article has been cited by other articles:

				J. S. Brown, H. Wessells, M. B. Chancellor, S. S. Howards, W. E. Stamm, A. E. Stapleton, W. D. Steers, S. K. Van Den Eeden, and K. T. McVary Urologic Complications of Diabetes Diabetes Care, January 1, 2005; 28(1): 177 - 185. [Full Text] [PDF]

				G. J. Christ, N. Day, C. Santizo, Y. Sato, W. Zhao, T. Sclafani, R. Bakal, M. Salman, K. Davies, and A. Melman Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1544 - H1553. [Abstract] [Full Text] [PDF]