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 b y 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 (AdCMVeNO S) into the corpora cavernosum of the aged rat. Adenoviral expression of th e beta-galactosidase reporter gene was observed in cavernosal tissue 1 day after intracavernosal administration of AdCMV beta gal; 1 day after adminis tration of AdCMVeNOS, transgene expression was confirmed by immunoblot stai ning of eNOS protein, and cGMP levels were increased. The increase in caver nosal 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 dono r sodium 1-(N,N-diethylamino) diazen-1-ium-1,2-diolate was not altered. The se results suggest that in vivo gene transfer of eNOS, alone or in combinat ion with a type V phosphodiesterase inhibitor, may constitute a new therape utic intervention for the treatment of erectile dysfunction.