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

Research output: Contribution to journalArticle

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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

Fingerprint

Gene transfer
Viral Genes
Rats
rho-Associated Kinases
Pressure
Arterial Pressure
Galactosidases
Penis
Sprague Dawley Rats
Maintenance
Chemical activation
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats. / Chitaley, Kanchan; Bivalacqua, Trinity J.; Champion, Hunter C.; Usta, Mustafa F.; Hellstrom, Wayne J G; Mills, Thomas M.; Webb, R Clinton.

In: Biochemical and Biophysical Research Communications, Vol. 298, No. 3, 25.11.2002, p. 427-432.

Research output: Contribution to journalArticle

Chitaley, Kanchan ; Bivalacqua, Trinity J. ; Champion, Hunter C. ; Usta, Mustafa F. ; Hellstrom, Wayne J G ; Mills, Thomas M. ; Webb, R Clinton. / Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 298, No. 3. pp. 427-432.
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