Increased corpus cavernosum smooth muscle tone associated with partial bladder outlet obstruction is mediated via Rho-kinase.
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 (ROKalpha and ROKbeta). 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.
Chang
Shaohua
S
Division of Urology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hypolite
Joseph A
JA
Zderic
Stephen A
SA
Wein
Alan J
AJ
Chacko
Samuel
S
Disanto
Michael E
ME
D000818:Animals; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009122:Muscle Hypertonia / Q000209:etiology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010413:Penis / Q000098:blood supply* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011817:Rabbits; D024745:Smooth Muscle Myosins / Q000378:metabolism*; D001748:Urinary Bladder Neck Obstruction / Q000150:complications / Q000503:physiopathology*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024745:Smooth Muscle Myosins