Improved erectile function after Rho-kinase inhibition in a rat castrate model of erectile dysfunction

Christopher J. Wingard, John A Johnson, Andre Holmes, Anita Prikosh

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Abstract

Androgens are reported to act as strong modulators of erectile function influencing both nitric oxide and vasoconstrictor signaling. Castration results in a depressed erectile response that is associated with a loss of nitric oxide production and increased responsiveness to constrictive agents. The increased vasoconstrictor response may be a result of an active RhoA/Rho-kinase signaling pathway. We report here results of studies designed to test the hypothesis that inhibition of the Rho-kinase pathway restores erectile function in a castrate model by relaxing the smooth muscle. Mean arterial (MAP) and corpus cavernosal (CCP) pressures were monitored during intracavernosal injection of the Rho-kinase inhibitor Y-27632. Castration reduced the maximal erectile response (CCP/MAP) by 33%, and testosterone replacement restored the response (intact, 0.736 ± 0.040; castrate, 0.492 ± 0.022; testosterone, 0.681 ± 0.073). Injection of Y-27632 increased CCP in all experimental groups; it also left shifted the voltage response curve and increased the maximal CCP/MAP response (intact, 0.753 ± 0.091; castrate, 0.782 ± 0.081; testosterone treated, 0.894 ± 0.033). Y-27632 dose dependently relaxed phenylephrinestimulated cavernosal tissues. Cavernosal tissues showed increased RhoA and Rho-kinase protein levels after castration. Our data support the hypothesis that an active Rho/Rho-kinase pathway contributes to the reduced erectile response after castration due to an upregulation of RhoA/Rho-kinase protein levels and that inhibition of this pathway may serve as an effective treatment for erectile dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume284
Issue number6 53-6
Publication statusPublished - Jun 1 2003

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Keywords

  • Corpus cavernosum
  • Phenylephrine
  • RhoA
  • Smooth muscle contraction
  • Testosterone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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