Bladder instability and detrusor smooth muscle function

Fry, Chris; Wu, Changhao; Mundy, Anthony R.

doi:10.1111/j.1469-445x.1999.tb00081.x

Cited by 15 publications

(15 citation statements)

References 19 publications

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“…28 -32 There was an apparent discordance between the absence of morphologically identifiable junctional structures on the one hand, and electrophysiologic data, which clearly indicated that current injected into one cell flows into neighboring cells. 13,33,34 Consistent with these electrophysiologic observations, recent studies have documented intercellular diffusion of hydrophilic dyes, such as Lucifer yellow, when injected (dialyzed) into detrusor Neurourology and Urodynamics DOI 10.1002/nau myocytes in situ. Furthermore, electron microscopy, immunogold labeling, confocal immunofluorescence, and Western blot techniques have all confirmed the presence of small junctional plaques comprised connexins (Cxs) between human detrusor myocytes.…”

Section: Intercellular Communicationmentioning

confidence: 55%

“…4,10 -12 It has been advocated that in the human detrusor, an inward flux of Ca 2þ is not physiologically important for initiation of mechanical activity since contraction is initiated by ACh and release of Ca 2þ from intracellular stores. 13,14 However, the spontaneous activity recorded in isolated detrusor preparations (including human) in isolated whole bladders, and during the bladder filling phase in vivo, should not be immediately dependent on ACh, which normally is released from nerves in vivo to produce a voiding contraction.…”

Section: Spontaneous Activation Of the Myocytementioning

confidence: 99%

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Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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Aims: To discuss (1) mechanisms involved in the generation and control of myocyte contractions and consequent afferent nerve activity and (2) these mechanisms as targets for drugs aimed for treatment of overactive bladder (OAB) symptoms and detrusor overactivity (DO). Methods: Literature review of myocyte activation, bladder afferent nerves, mediators in the bladder, and translational aspects of the findings. Results: During bladder filling, there is normally no parasympathetic outflow from the spinal cord. Despite this, the bladder develops tone during filling and also exhibits non-synchronized local contractions and relaxations that are caused by a basal myogenic mechanical activity that may be reinforced by release of, for example, acetylcholine from non-neuronal and/or neuronal sources or local mediators, such as prostaglandins and endothelins. It is suggested that these spontaneous contractions are able to generate activity in afferent nerves (''afferent noise'') that may contribute to DO and OAB. Conclusions: Spontaneous bladder myocyte contractions and factors that are able to modulate them, as well as the consequent afferent nerve activity, may be targets for drugs meant for treatment of OAB/DO. Neurourol.

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Section: Intercellular Communicationmentioning

confidence: 55%

Section: Spontaneous Activation Of the Myocytementioning

confidence: 99%

Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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“…can a¡ect the rate of tension generation before a¡ecting the maximal tension developed [Levin et al, 1997;Geloso and Levin, 1998;Fry et al, 1999]. The time to maximal tension in response to FS is related to the release of transmitters, di¡u-sion across the synapse, activation of postsynaptic receptors, and release and di¡usion of calcium within the smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of Doxazosin on rat urinary bladder function after partial outlet obstruction

Das

Leggett

Whitbeck

et al. 2002

Neurourology and Urodynamics

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Hypoxia induced by partial outlet obstruction is believed to play a major role in both the hypertrophic and degenerative effects of partial outlet obstruction. Doxazosin (dox) is a clinically effective alpha-adrenergic antagonist used in the treatment of symptomatic benign prostatic hyperplasia (BPH). Although the major therapeutic effect of the agent is believed to occur on the smooth muscle components of the prostate by reducing prostatic urethral resistance and thus improving emptying, dox may have part of its clinical action via effects mediated by other actions, including via spinal alpha-adrenergic receptors or direct effects on the bladder, possibly via inhibition of vascular alpha receptors. The specific aim of the current study was to determine whether dox pretreatment on rats affects blood flow to the bladder and reduces the level of bladder dysfunction induced by partial outlet obstruction. In part 1, eight rats were separated into two groups of four rats each. Group 1 received oral administration of dox (30 mg/kg) for 4 weeks; group 2 received vehicle (5% dimethyl sulfoxide). After 4 weeks of treatment, blood flow studies were performed using fluorescent microspheres and the bladders excised, frozen, and submitted to Interactive Medical Technologies (IMT) for blood flow analysis. In part 2, 32 adult male rats were separated into four groups of eight rats each. Groups 1 and 2 received oral administration of dox (30 mg/kg) for 4 weeks, groups 3 and 4 received vehicle (5% dimethyl sulfoxide). At 4 weeks, the rats in groups 1 and 3 received partial outlet obstructions and treatment continued for an additional 2 weeks. After 6 weeks of treatment (total), each rat was anesthetized, the bladder excised, weighed, and isolated strips mounted and contractility studies performed. 1) Four weeks pretreatment of rats with dox increased blood flow to the bladder in both the control and obstructed groups. 2) Partial outlet obstruction induced a mild decrease in blood flow. 3) The magnitude of the increased bladder weight in the vehicle-treated obstructed group was significantly greater than in the dox-treated obstructed group. 4) Partial outlet obstruction resulted in significant decreases in the contractile response to field stimulation in both treated and non-treated rats. The magnitude of the decreased response was significantly greater in the non-treated rats. 5) The response to potassium chloride was significantly reduced by partial outlet obstruction in the vehicle-treated group but not in the dox-treated group. 6) The time to maximal tension was significantly increased in response to carbachol, adenosine triphosphate, and potassium chloride. However, the magnitude of the increase was significantly greater for the vehicle-treated obstructed groups stimulated by potassium chloride than for the dox-treated groups. Dox treatment of rats increased blood flow to the bladder and reduced the severity of the response to partial outlet obstruction. These beneficial effects would be due to pharmacological effects on alph...

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“…Briefly, the space constant () for decremental current flow measured in detrusor smooth muscle is Ϸ1 mm, compared with a cell length of 150-200 m. Such a 5-to 10-fold difference between the space constant for passive current decay and cell length is a clear indication of the presence of an adequate intercellular pathway (9,(23)(24)(25). Although the resistance of the intercellular pathway in the bladder is clearly much larger than that observed in organs known to be well coupled (e.g., myocardium) (13,23), the membrane resistance of the detrusor myocyte is also correspondingly greater (e.g., than a cardiac myocyte), so that overall, the R m /R i still favors significant intercellular current flow.…”

Section: Discussionmentioning

confidence: 99%

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

Christ

Day²,

Day³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

101

111

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Bladder overactivity associated with outflow obstruction is a common human condition recapitulated in the female rat by narrowing the diameter of the urethra. The goal of these studies was to evaluate the role of intercellular communication through connexin43 (Cx43)-derived gap junction channels to bladder overactivity following partial urethral outflow obstruction of 3-day to 6-wk duration. Cx43 mRNA and protein expression were barely detectable by Northern or Western blots, respectively, in the detrusor layer of normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed a statistically significant positive correlation between the duration of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43 mRNA transcript levels, such that after 6 wk of obstruction, Cx43 transcript levels were ≈15-fold greater than initial control values. When taking into account the approximately fivefold increase in bladder weight over this same time frame, the absolute amount of Cx43 mRNA in the bladder apparently increased by ≈75-fold. In that regard, as anticipated, and consistent with previous observations, 6 wk of obstruction was also associated with a significant increase in spontaneous bladder contractions between micturitions. The amplitude of these contractions was significantly reduced by heptanol given intravesically. Furthermore, carbachol-precontracted bladder strips from obstructed animals were more sensitive to heptanol-induced relaxation (100 μM) than their unobstructed counterparts ( n = 6; P < 0.01). When bladder strips were equivalently precontracted via electrical field stimulation (EFS; 20 Hz), similar heptanol-induced relaxation responses were observed. However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than unobstructed bladders ( n = 7; P < 0.01). Taken together, these observations indicate that partial outlet obstruction produces an overactive bladder that may be more dependent on intercellular communication through gap junctions for modulation of contractile responses than its normal counterpart.

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Bladder instability and detrusor smooth muscle function

Cited by 15 publications

References 19 publications

Detrusor myocyte activity and afferent signaling

Detrusor myocyte activity and afferent signaling

Effect of Doxazosin on rat urinary bladder function after partial outlet obstruction

Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

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