Gene Transfer of Endothelial Nitric Oxide Synthase to the Penis Augments Erectile Responses in the Aged Rat

Nitric oxide (NO), a mediator involved in penile erection, is synthesized by the nitric oxide synthase (NOS) family of enzymes. It has been shown that NOS activity decreases with age. To determine whether adenoviral-mediated overexpression of endothelial NOS (eNOS) could enhance erectile responses,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-09, Vol.96 (20), p.11648-11652
Main Authors: Champion, H C, Bivalacqua, T J, Hyman, A L, Ignarro, L J, Hellstrom, W J, Kadowitz, P J
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Adenoviridae - genetics
Adenovirus
Adenoviruses
Aging - physiology
Animals
Biological Sciences
Blood plasma
Cyclic GMP - analysis
Electric Stimulation
eNOS gene
Enzymes
Erectile Dysfunction - therapy
Gene Transfer Techniques
Genetic Therapy
Male
Nerves
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - physiology
Nitric Oxide Synthase Type III
Oxides
Penile erection
Penis - metabolism
Pharmacology
Purinones - pharmacology
Rats
Rats, Sprague-Dawley
Sodium
sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate
Transfection
Vehicles
zaprinast
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Summary:Nitric oxide (NO), a mediator involved in penile erection, is synthesized by the nitric oxide synthase (NOS) family of enzymes. It has been shown that NOS activity decreases with age. To determine whether adenoviral-mediated overexpression of endothelial NOS (eNOS) could enhance erectile responses, we administered a recombinant adenovirus containing the eNOS gene (AdCMVeNOS) into the corpora cavernosum of the aged rat. Adenoviral expression of the β -galactosidase reporter gene was observed in cavernosal tissue 1 day after intracavernosal administration of AdCMVβ gal; 1 day after administration of AdCMVeNOS, transgene expression was confirmed by immunoblot staining of eNOS protein, and cGMP levels were increased. The increase in cavernosal pressure in response to cavernosal nerve stimulation was enhanced in animals transfected with eNOS, and erectile responses to acetylcholine and zaprinast were enhanced at a time when the erectile response to the NO donor sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate was not altered. These results suggest that in vivo gene transfer of eNOS, alone or in combination with a type V phosphodiesterase inhibitor, may constitute a new therapeutic intervention for the treatment of erectile dysfunction.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.20.11648