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

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.20.11648

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.