title: Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats.
abstract: We previously reported the inhibition of Rho-kinase to result in increased intracavernosal pressure (ICP) in an in vivo rat model of erection. Expression of an upstream activator of Rho-kinase, RhoA, has been demonstrated in the penile vasculature; however, the functional role of RhoA in the regulation of erection remains unknown. We used adeno-associated viral gene transfer of a dominant negative RhoA mutant (T19NRhoA) into rat cavernosum to test the hypothesis that RhoA activation is physiologically important for maintenance of the non-erect state and inhibition of this pathway leads to erection. Anesthetized, male, Sprague-Dawley rats transfected with the T19NRhoA mutant exhibited an elevated baseline ICP/mean arterial pressure (MAP) and nerve stimulation-induced ICP/MAP as compared with beta-galactosidase-transfected controls. The novel findings of this study demonstrate a functional role of RhoA in maintaining the flaccid penis and provide support for the inhibition of RhoA as a potential therapy for the enhancement of erectile function.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA. kanchanc@u.washington.edu
authors.forename: Kanchan
authors.initials: K
authors.lastname: Chitaley
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Mustafa F
authors.initials: MF
authors.lastname: Usta
authors.forename: Wayne J G
authors.initials: WJ
authors.lastname: Hellstrom
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mills
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D008297:Male; D010410:Penile Erection / Q000235:genetics*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D020742:rhoA GTP-Binding Protein