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

Kanchan Chitaley, Trinity J. Bivalacqua, Hunter C. Champion, Mustafa F. Usta, Wayne J.G. Hellstrom, Thomas M. Mills, R. Clinton Webb

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59 Scopus citations

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 β-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.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume298
Issue number3
DOIs
StatePublished - Nov 25 2002

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Keywords

  • Cavernosal
  • Erectile dysfunction
  • Erection
  • Gene therapy
  • Rho-kinase
  • Vasoconstriction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chitaley, K., Bivalacqua, T. J., Champion, H. C., Usta, M. F., Hellstrom, W. J. G., Mills, T. M., & Clinton Webb, R. (2002). Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats. Biochemical and Biophysical Research Communications, 298(3), 427-432. https://doi.org/10.1016/S0006-291X(02)02458-0