scholarly journals Adjustable passive stiffness in mouse bladder: regulated by Rho kinase and elevated following partial bladder outlet obstruction

2012 ◽  
Vol 302 (8) ◽  
pp. F967-F976 ◽  
Author(s):  
John E. Speich ◽  
Jordan B. Southern ◽  
Sheree Henderson ◽  
Cameron W. Wilson ◽  
Adam P. Klausner ◽  
...  
Keyword(s):  
Bladder Outlet Obstruction ◽  
Bladder Wall ◽  
Rho Kinase ◽  
Outlet Obstruction ◽  
Prostaglandin E ◽  
Passive Stiffness ◽  
Regulatory Pathways ◽  
Partial Bladder Outlet Obstruction ◽  
Length Changes ◽  
Adjustable Passive Stiffness

Detrusor smooth muscle (DSM) contributes to bladder wall tension during filling, and bladder wall deformation affects the signaling system that leads to urgency. The length-passive tension ( L-Tp) relationship in rabbit DSM can adapt with length changes over time and exhibits adjustable passive stiffness (APS) characterized by a L-Tpcurve that is a function of both activation and strain history. Muscle activation with KCl, carbachol (CCh), or prostaglandin E2at short muscle lengths can increase APS that is revealed by elevated pseudo-steady-state Tpat longer lengths compared with prior Tpmeasurements at those lengths, and APS generation is inhibited by the Rho Kinase (ROCK) inhibitor H-1152. In the current study, mouse bladder strips exhibited both KCl- and CCh-induced APS. Whole mouse bladders demonstrated APS which was measured as an increase in pressure during passive filling in calcium-free solution following CCh precontraction compared with pressure during filling without precontraction. In addition, CCh-induced APS in whole mouse bladder was inhibited by H-1152, indicating that ROCK activity may regulate bladder compliance during filling. Furthermore, APS in whole mouse bladder was elevated 2 wk after partial bladder outlet obstruction, suggesting that APS may be relevant in diseases affecting bladder mechanics. The presence of APS in mouse bladder will permit future studies of APS regulatory pathways and potential alterations of APS in disease models using knockout transgenetic mice.

Long term partial bladder outlet obstruction induced contractile dysfunction in male rabbits: A role for Rho-kinase

2007 ◽  
Vol 26 (7) ◽  
pp. 1043-1049 ◽  
Author(s):  
Ahmet Guven ◽  
Bulent Onal ◽  
Carmin Kalorin ◽  
Catherine Whitbeck ◽  
Paul Chichester ◽  
...  
Keyword(s):  
Bladder Outlet Obstruction ◽  
Rho Kinase ◽  
Outlet Obstruction ◽  
Contractile Dysfunction ◽  
Partial Bladder Outlet Obstruction

The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho-kinase in rabbits

2008 ◽  
Vol 27 (8) ◽  
pp. 826-831 ◽  
Author(s):  
Wei-Yu Lin ◽  
Anita Mannikarottu ◽  
Paul Chichester ◽  
Paul Neuman ◽  
Arnold Johnson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Corpus Cavernosum ◽  
Rho Kinase ◽  
Outlet Obstruction ◽  
Partial Bladder Outlet Obstruction

Deletion of one SERCA2 allele confers protection against bladder wall hypertrophy in a murine model of partial bladder outlet obstruction

2008 ◽  
Vol 294 (1) ◽  
pp. R58-R65 ◽  
Author(s):  
Jenny Lassmann ◽  
Joanna Sliwoski ◽  
Andy Chang ◽  
Douglas A. Canning ◽  
Stephen A. Zderic
Keyword(s):  
Murine Model ◽  
Bladder Outlet Obstruction ◽  
Nuclear Translocation ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Wild Type ◽  
Compensatory Mechanisms ◽  
Activated T Cells ◽  
Significant Drop ◽  
Partial Bladder Outlet Obstruction

The sarco(endo)plasmic reticulum Ca2+-ATPase2 (SERCA2) is downregulated in cardiac hypertrophy with decompensation. We sought to determine whether mice heterozygous for the SERCA2 allele would develop greater bladder hypertrophy and decompensation than their wild-type littermates following partial bladder outlet obstruction (pBOO). We found that following 4 wk of surgically created pBOO, SERCA2 heterozygous murine bladders showed significantly less hypertrophy, improved in vitro cystometry performance, diminished expression of the slow myosin isoform A analyzed by RT-PCR, a significant drop in nuclear translocation of nuclear factor of activated T cells by EMSA, and decreased cell proliferation within the smooth muscle layer following 5-bromo-2′-deoxyuridine labeling compared with their wild-type littermates. Thus, in contrast to cardiac muscle, deletion of a SERCA2 allele confers protection against bladder hypertrophy in a murine model of pBOO. Compensatory mechanisms in heterozygous mice seem to be related to the calcineurin pathway. Further studies are underway to better define the molecular basis of this observation, which has potential clinical applications.

scholarly journals Effect of Age on the Role of Rho-Kinase in Short-term Partial Bladder Outlet Obstruction

Urology ◽  
2008 ◽  
Vol 71 (3) ◽  
pp. 541-545 ◽  
Author(s):  
Ahmet Guven ◽  
Wei-Yu Lin ◽  
Paul Neuman ◽  
Barry A. Kogan ◽  
Robert Levin ◽  
...  
Keyword(s):  
Bladder Outlet Obstruction ◽  
Rho Kinase ◽  
Outlet Obstruction ◽  
Short Term ◽  
Partial Bladder Outlet Obstruction ◽  
Effect Of Age

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

2005 ◽  
Vol 289 (4) ◽  
pp. R1124-R1130 ◽  
Author(s):  
Shaohua Chang ◽  
Joseph A. Hypolite ◽  
Stephen A. Zderic ◽  
Alan J. Wein ◽  
Samuel Chacko ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Rabbit Model ◽  
Corpus Cavernosum ◽  
Rho Kinase ◽  
Outlet Obstruction ◽  
Smooth Muscle Myosin ◽  
Partial Bladder Outlet Obstruction ◽  
Kinase Expression ◽  
Muscle Myosin

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 (ROKα and ROKβ). 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.

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