Strain Induced Bladder Smooth Muscle Remodeling

2007 ◽  
Author(s):  
Rebecca A. Long ◽  
Aron Parekh ◽  
Michael S. Sacks
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Bladder Function ◽  
Compensatory Mechanism ◽  
Bladder Smooth Muscle ◽  
Cord Injury

Multiple urinary bladder wall (UBW) pathologies, such as overactive bladder, bladder outlet obstruction, spinal cord injury (SCI) and related neurogenic disorders, and diabetes result in tissue remodeling marked by hypertrophic bladder smooth muscle cells (BSMC) and altered extra-cellular matrix components. This remodeling results in changes in UBW biomechanical properties leading to altered bladder function. Our previous studies have revealed that during the initial areflexic phase of SCI the UBW undergoes profound remodeling that appears to be a compensatory mechanism for the increased wall stretch resulting from over-distension [1, 2]. Remodeling in the bladder wall results in changes in biomechanics and ultimately the ability of the organ to normally fill and void [3]. The stimuli and precise mechanisms that are responsible for bladder remodeling in SCI and the aforementioned pathologies remain unknown. The objective of the present study is to determine the effects of varied in vitro strain on ECM production in the ex vivo rat bladder as a first step toward understanding tissue remodeling in response to strain.

scholarly journals Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

2017 ◽  
Vol 44 (3) ◽  
pp. 907-919 ◽  
Author(s):  
Qiang Liu ◽  
Deyi Luo ◽  
Tongxin Yang ◽  
Banghua Liao ◽  
Hong Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Structure And Function ◽  
Bladder Function ◽  
Bladder Smooth Muscle ◽  
M3 Receptors ◽  
And Function

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

scholarly journals Urinary Bladder Contraction and Relaxation: Physiology and Pathophysiology

2004 ◽  
Vol 84 (3) ◽  
pp. 935-986 ◽  
Author(s):  
Karl-Erik Andersson ◽  
Anders Arner
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Hormonal Control ◽  
Membrane Properties ◽  
Bladder Function ◽  
Future Research ◽  
Detrusor Smooth Muscle ◽  
Functional Changes

The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.

scholarly journals Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: Attenuation of purinergic bladder smooth muscle contractions.

2021 ◽  
Author(s):  
Nagat Frara ◽  
Dania Giaddui ◽  
Alan S Braverman ◽  
Danielle S. Porreca ◽  
Justin M Brown ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Purinergic Receptor ◽  
Muscle Contractions ◽  
Bladder Function ◽  
Detrusor Muscle ◽  
Bladder Smooth Muscle ◽  
Contractile Responses ◽  
Smooth Muscle Contractions

This study determined the effect of pelvic organ decentralization and reinnervation one year later on the contribution of muscarinic and purinergic receptors to ex-vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. After exclusions, 8 were reinnervated 12 months post-decentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 months later; four served as long-term decentralized only animals. Controls included six sham-operated and three unoperated animals. Detrusor muscle was assessed for contractile responses to potassium chloride (KCl) and electric field stimulation (EFS) before and after purinergic receptor desensitization with alpha, beta-methylene adenosine triphosphate (α,β-mATP), muscarinic receptor antagonism with atropine, or sodium channel blockade with tetrodotoxin. Atropine inhibition of EFS-induced contractions increased in decentralized and reinnervated animals compared to controls. Maximal contractile responses to α,β-mATP did not differ between groups. In strips from decentralized and reinnervated animals, the contractile response to EFS was enhanced at lower frequencies compared to normal controls. The observation of increased blockade of nerve-evoked contractions by muscarinic antagonist with no change in responsiveness to purinergic agonist suggests either decreased ATP release or increased ecto-ATPase activity in detrusor muscle as a consequence of the long-term decentralization. The reduction in the frequency required to produce maximum contraction following decentralization may be due to enhanced nerve sensitivity to EFS or a change in the effectiveness of the neurotransmission.

scholarly journals Mechanical stretch upregulates proteins involved in Ca2+sensitization in urinary bladder smooth muscle hypertrophy

2014 ◽  
Vol 307 (6) ◽  
pp. C542-C553 ◽  
Author(s):  
Ettickan Boopathi ◽  
Cristiano Gomes ◽  
Stephen A. Zderic ◽  
Bruce Malkowicz ◽  
Ranjita Chakrabarti ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Hypertrophy ◽  
Type I Collagen ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Mechanical Stretch ◽  
Transcriptional Level ◽  
Type I ◽  
Bladder Smooth Muscle ◽  
Cell Stretch

Partial bladder outlet obstruction (pBOO)-induced remodeling of bladder detrusor smooth muscle (DSM) is associated with the modulation of cell signals regulating contraction. We analyzed the DSM from obstructed murine urinary bladders for the temporal regulation of RhoA GTPase and Rho-activated kinase (ROCK), which are linked to Ca2+sensitization. In addition, the effects of equibiaxial cell stretch, a condition thought to be associated with pBOO-induced bladder wall smooth muscle hypertrophy and voiding frequency, on the expression of RhoA, ROCK, and C-kinase-activated protein phosphatase I inhibitor (CPI-17) were investigated. DSM from 1-, 3-, 7-, and 14-day obstructed male mice bladders and benign prostatic hyperplasia (BPH)-induced obstructed human bladders revealed overexpression of RhoA and ROCK-β at the mRNA and protein levels compared with control. Primary human bladder myocytes seeded onto type I collagen-coated elastic silicone membranes were subjected to cyclic equibiaxial stretch, mimicking the cellular mechanical stretch in the bladder in vivo, and analyzed for the expression of RhoA, ROCK-β, and CPI-17. Stretch caused a significant increase of RhoA, ROCKβ, and CPI-17 expression. The stretch-induced increase in CPI-17 expression occurs at the transcriptional level and is associated with CPI-17 promoter binding by GATA-6 and NF-κB, the transcription factors responsible for CPI-17 gene transcription. Cell stretch caused by bladder overdistension in pBOO is the likely mechanism for initiating overexpression of the signaling proteins regulating DSM tone.

scholarly journals NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11684
Author(s):  
Xiang Xie ◽  
Chuang Luo ◽  
Jia Yu Liang ◽  
Run Huang ◽  
Jia Li Yang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Overactive Bladder ◽  
Bladder Wall ◽  
Bladder Function ◽  
Wild Type ◽  
Bladder Smooth Muscle ◽  
Aspartate Receptor ◽  
The Common ◽  
And Function ◽  
Common Pathogenesis

Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle–specific NMDAR knockout (SMNRKO) mouse model was generated. The bladders from SMNRKO mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, SMNRKO mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated SMNRKO and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, SMNRKO mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and SMNRKO mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.

scholarly journals Gene expression profiles during tissue remodeling following bladder outlet obstruction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saya Ito ◽  
Takeshi Nomura ◽  
Takashi Ueda ◽  
Shogo Inui ◽  
Yukako Morioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Expression Patterns ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Mrna Levels ◽  
Muscular Hypertrophy ◽  
Bladder Smooth Muscle ◽  
Urinary Function

AbstractBladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.

scholarly journals Engineered Stem Cells Improve Neurogenic Bladder by Overexpressing SDF-1 in a Pelvic Nerve Injury Rat Model

2020 ◽  
Vol 29 ◽  
pp. 096368972090246 ◽  
Author(s):  
Guan Qun Zhu ◽  
Seung Hwan Jeon ◽  
Kyu Won Lee ◽  
Hyuk Jin Cho ◽  
U-Syn Ha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Neurogenic Bladder ◽  
Rat Model ◽  
Bladder Wall ◽  
Bladder Function ◽  
Pelvic Nerve ◽  
Injured Nerve

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1+) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1−). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1+, imMSCs/eSDF-1−, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1+ expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1+ improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1+ group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1+ group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1+ group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

Mechanisms of bladder smooth-muscle hypertrophy and decompensation: lessons from normal development and the response to outlet obstruction

1998 ◽  
Vol 16 (5) ◽  
pp. 350-358 ◽  
Author(s):  
Stephen A. Zderic ◽  
Alan Wein ◽  
Dorothea Rohrman ◽  
ChiaoLiang Gong ◽  
Denise Nigro ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Hypertrophy ◽  
Normal Development ◽  
Outlet Obstruction ◽  
Bladder Smooth Muscle
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