Journal article
Activated RhoA/Rho Kinase Impairs Erectile Function After Cavernous Nerve Injury in Rats
The Journal of urology, Vol.184(5), pp.2197-2204
2010
DOI: 10.1016/j.juro.2010.06.094
PMID: 20851436
Abstract
RhoA and rho kinase serve as key regulators of penile vascular homeostasis. The role of RhoA/rho kinase signaling in the penis after cavernous nerve injury has not been fully investigated. We characterized the molecular expression profiles of RhoA/rho kinase signaling that occur in the penis after cavernous nerve injury. We hypothesized that erectile dysfunction after bilateral cavernous nerve injury is accompanied by up-regulation of RhoA/rho kinase activity in the rat penis.
We used 2 groups, including sham operation and bilateral cavernous nerve injury. At 14 days after nerve injury each group underwent cavernous nerve stimulation to determine erectile function at baseline and after intracavernous injection of the rho kinase inhibitor Y-27632 (Tocris Bioscience, Ellisville, Missouri). Penes were assessed at baseline for protein expression of neuronal nitric oxide synthase, RhoA, and rho kinase 1 and 2 by Western blot, immunoreactivity of neuronal nitric oxide synthase, rho kinase 1 and 2, RhoA-guanosine triphosphatase and rho kinase activity.
Erectile function was decreased in nerve injured rats. Neuronal nitric oxide synthase protein was significantly decreased while RhoA and rho kinase 2 protein levels were significantly increased in rat penes with nerve injury. Rho kinase 1 protein expression was equivalent. Rho kinase immunoreactivity was qualitatively increased in the corporeal smooth muscle of nerve injured rats. RhoA-guanosine triphosphatase and rho kinase activity was significantly increased in injured rat penes compared to that in sham operated penes. Intracavernous injection of Y-27632 caused a significantly greater increase in intracavernous pressure in nerve injured rats compared to that in sham operated rats, suggesting increased rho kinase activity.
Data suggest that RhoA/rho kinase up-regulation in response to cavernous nerve injury contributes to penile vasculature dysfunction after cavernous nerve injury. Thus, the RhoA/rho kinase pathway may be a suitable target for treating post-radical prostatectomy erectile dysfunction.
Details
- Title: Subtitle
- Activated RhoA/Rho Kinase Impairs Erectile Function After Cavernous Nerve Injury in Rats
- Creators
- Christian Gratzke - Ludwig-Maximilians-Universität MünchenTravis D. Strong - Johns Hopkins UniversityMilena A. Gebska - University of IowaHunter C. Champion - University of Pittsburgh Medical CenterChristian G. Stief - Ludwig-Maximilians-Universität MünchenArthur L. Burnett - Johns Hopkins UniversityTrinity J. Bivalacqua - Johns Hopkins University
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.184(5), pp.2197-2204
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.juro.2010.06.094
- PMID
- 20851436
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Grant note
- German Society of Andrology European Society of Sexual Medicine Grant for Medical Research American Urological Association Foundation Astellas USA Foundation MD/PhD Grant
- Language
- English
- Date published
- 2010
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359876602771
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