The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho-kinase in rabbits.
OBJECTIVE
The goal of this study was to investigate the effect of different severities in bladder dysfunction on corpus cavernosum physiology, morphology and expression of Rho-kinase in rabbits.


METHODS
Male New Zealand rabbits were divided into control, 2 and 8 weeks of partial bladder outlet obstruction (PBOO) groups. Isolated cavernosal strips from all groups were precontracted with phenylephrine and the relaxant responses to electrical field stimulation (EFS), ATP, acetylcholine, and sodium nitroprusside (SNP) were determined. Histological and molecular studies were performed.


RESULTS
Corpus cavernosum smooth muscle (CCSM) from 8 weeks obstruction rabbits showed significant decreases in the contractile response to phenylephrine and further decreased relaxation responses to EFS in comparison to 2 weeks group. Relaxation induced by ATP, acetylcholine, and SNP were all significantly diminished at both 2 and 8 weeks obstruction equally. The ratio of smooth muscle to collagen decreased at 2 weeks and further dropped at 8 weeks obstruction. Expression of both isoforms of Rho-kinase were increased in both obstruction groups at 2 weeks obstruction and decreased significantly (from the 2 week obstructed values) at 8 weeks while remaining above control values.


CONCLUSIONS
The present study indicated that severe bladder dysfunction secondary to chronic PBOO induced significant physiological dysfunctions of CCSM as well as morphological changes. Activities of both ROK isoenzymes showed increases at 2- and 8-week obstructions. Increase in Rho-kinase expression/activity would be expected to make the CCSM more difficult to relax and also contribute to reduction of EFS-induced relaxation of CCSM after chronic PBOO.
Division of Urology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Chia-Yi, Taiwan, ROC.
Wei-Yu
WY
Lin
Anita
A
Mannikarottu
Paul
P
Chichester
Paul
P
Neuman
Arnold
A
Johnson
Francisco C
FC
Pérez-Martínez
Robert M
RM
Levin
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007527:Isoenzymes; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012720:Severity of Illness Index; D013997:Time Factors; D001748:Urinary Bladder Neck Obstruction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000378:metabolism*
D007527:Isoenzymes; D009599:Nitroprusside; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D003094:Collagen; D054460:rho-Associated Kinases; D000109:Acetylcholine