Long term partial bladder outlet obstruction induced contractile dysfunction in male rabbits: a role for Rho-kinase.
OBJECTIVE
In this study we examined the expression of Rho-kinase (ROK) isoforms in rabbit detrusor smooth muscle during the progression of partial bladder outlet obstruction and correlated them with the time course of obstruction.


METHODS
Detrusor samples were obtained from bladders after 1, 2, 4, and 8 weeks of obstruction and also sham operated control rabbits. Contractile responses to field stimulation (FS) and also the smooth muscle (SM) to collagen ratio were determined in isolated bladder strips. Reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to determine the relative levels of ROK isoform expression at the mRNA and protein levels.


RESULTS
Bladder weight increased gradually and contractile responses were reduced significantly over the course of obstruction. The smooth muscle/collagen ratio increased significantly during the course of obstruction. The expression of ROKalpha increased significantly to approximately the same extent in 1-4-week obstructed groups and increased further in the 8-week obstructed group, both at the mRNA and protein levels. In contrast, there was a significant decrease in the expression of ROKbeta in the obstructed groups, which gradually decrease during the course of 1-4-week obstruction period and are slightly upregulated at the decompensated stage at 8-week obstruction.


CONCLUSIONS
The change in the isoforms of ROK may be part of the molecular mechanism for bladder compensation following partial bladder outlet obstruction.
Guven
Ahmet
A
Section of Pediatric Urology, Albany Medical College, Albany, New York, USA.
Onal
Bulent
B
Kalorin
Carmin
C
Whitbeck
Catherine
C
Chichester
Paul
P
Kogan
Barry
B
Levin
Robert
R
Mannikarottu
Anita
A
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000201:enzymology* / Q000503:physiopathology*; D011817:Rabbits; D013997:Time Factors; D001743:Urinary Bladder / Q000201:enzymology / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000378:metabolism*
D015415:Biomarkers; D007527:Isoenzymes; D003094:Collagen; D054460:rho-Associated Kinases