HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/R1124    most recent 00717.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Chang, S. Articles by DiSanto, M. E. Search for Related Content PubMed PubMed Citation Articles by Chang, S. Articles by DiSanto, M. E.

WATER AND ELECTROLYTE HOMEOSTASIS

Increased corpus cavernosum smooth muscle tone associated with partial bladder outlet obstruction is mediated via Rho-kinase

¹Division of Urology and ²Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania; and ³Division of Urology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Submitted 16 December 2003 ; accepted in final form 10 June 2005

Numerous studies have now demonstrated that lower urinary tract symptoms (LUTS) are associated with erectile dysfunction (ED) in men independent of age or general health. Because one-third of men over the age of 50 will develop LUTS and a recent study showed ED in 62% of patients presenting for LUTS, the importance of determining the mechanistic link between these two pathologies is clear. Using a rabbit model of partial bladder outlet obstruction (PBOO), a primary cause of LUTS, we have identified an increased basal corpus cavernosum smooth muscle (CCSM) tone associated with an elevated level of smooth muscle myosin (SMM) phosphorylation in PBOO compared with sham-operated control rabbits (sham). Results from in vitro kinase and phosphatase assays using purified smooth muscle myosin showed increased kinase and decreased phosphatase activities in cellular extracts from corpora cavernosa isolated from PBOO compared with sham rabbits. Increased Rho-kinase expression in the CCSM of PBOO rabbits was suggested by the observations that Rho-kinase inhibitors attenuated the increased kinase activity and were less effective in relaxing CCSM strips from PBOO vs. sham rabbits. This hypothesis was then confirmed by RT-PCR and Western blotting, which demonstrated increased expression of both isoforms of Rho-kinase (ROK and ROK). Increased SMM basal phosphorylation (necessary for SM contraction) in the CCSM of PBOO rabbits, mediated via an increase in Rho-kinase expression/activity, would be expected to make the CCSM more difficult to relax (necessary for erection), which suggests that the RhoA/Rho-kinase pathway as being involved in the mechanism for LUTS-associated ED.

lower urinary tract symptoms; erectile dysfunction; corpus cavernosum; smooth muscle myosin phosphorylation; Y-27632

This article has been cited by other articles:

				W.-Y. Lin, A. Mannikarottu, P. Chichester, A. Guven, A. Johnson, P. Neuman, Y.-S. Juan, C. Schuler, B. Kogan, and R. M. Levin Changes in the Smooth Muscle of the Corpora Cavernosum Related to Reversal of Partial Bladder Outlet Obstruction in Rabbits J Androl, March 1, 2008; 29(2): 164 - 171. [Abstract] [Full Text] [PDF]