Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats

Author: Chitaley K.   Bivalacqua T.J.   Champion H.C.   Usta M.F.   Hellstrom W.J.G.   Mills T.M.   Clinton Webb R.  

Publisher: Elsevier

ISSN: 0006-291X

Source: Biochemical and Biophysical Research Communications, Vol.298, Iss.3, 2002-11, pp. : 427-432

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

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 withβ-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.© 2002 Elsevier Science (USA)