Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats.
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.
Chitaley
Kanchan
K
Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA. kanchanc@u.washington.edu
Bivalacqua
Trinity J
TJ
Champion
Hunter C
HC
Usta
Mustafa F
MF
Hellstrom
Wayne J G
WJ
Mills
Thomas M
TM
Webb
R Clinton
RC
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*
D020742:rhoA GTP-Binding Protein