Open AccessGene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat
Author(s) -
Hunter C. Champion,
Trinity J. Bivalacqua,
Albert L. Hyman,
L. J. Ignarro,
Wayne J.G. Hellstrom,
Philip J. Kadowitz
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.20.11648
Subject(s) - enos , nitric oxide , nitric oxide synthase , erectile dysfunction , nitric oxide synthase type iii , medicine , endocrinology , stimulation , penis , zaprinast , sodium nitroprusside , biology , anatomy , guanylate cyclase
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 AdCMVβgal; 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 thatin 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.