Diabetic plasticity of non-adrenergic non-cholinergic and P2X-mediated rat bladder contractions.

We investigated the plasticity effects of diabetes mellitus and diuresis on the non-adrenergic non-cholinergic (NANC) and purinergic (P2X-type) contractile responses in longitudinal rat bladder strips. Female Sprague-Dawley rats received streptozotocin to induce diabetes, or sucrose in water to induce diuresis as a control condition for polyuria. Experiments were carried out at four weeks after treatments, using bladders from non-treated rats as control.

Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors.

Objective: To evaluate the role of bladder sensory purinergic P2X3 and P2X2/3 receptors on modulating the activity of lumbosacral neurones and urinary bladder contractions in vivo in normal or spinal cord-injured (SCI) rats with neurogenic bladder overactivity.

Materials And Methods: SCI was induced in female rats by complete transection at T8-T9 and experiments were performed 4 weeks later, when bladder overactivity developed. Non-transected rats were used as controls (normal rats).

Lumbosacral sensory neuronal activity is enhanced by activation of urothelial purinergic receptors.

Urothelial purinergic receptors are important for the regulation of afferent sensory pathways in bladder pain and overactivity. Using in vivo electrophysiological recordings we evaluated the activity of spinal dorsal horn neurons in female rats at the L6/S1 level when urinary bladder pressure was abruptly increased. Intravesical infusion of ATP and systemic application of suramin allowed us to evaluate the contribution of urothelial purinergic receptors.

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury.

The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T(9)-T(10) spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine.

Central inhibitory effect of intravesically applied botulinum toxin A in chronic spinal cord injury.

Aims: We evaluated a putative central inhibitory effect of intravesical botulinum toxin A (BoNT-A) on the activity of lumbosacral spinal neurons in a chronic spinal cord injury (SCI) model of bladder overactivity.

Methods: Female Sprague-Dawley rats underwent T8 spinal cord transection. Four weeks later, once overactive neuropathic detrusor pathways had developed, the animals underwent intravesical instillation with either saline (1 ml) or BoNT-A (Botox®, 20 U/1 ml) for 1 hr.

Overactive and underactive bladder dysfunction is reflected by alterations in urothelial ATP and NO release.

ATP and NO are released from the urothelium in the bladder. Detrusor overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in (1) early diabetic bladders, an overactive bladder model; and (2) "diuretic" bladders, an underactive bladder model.

Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder.

Background: The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium.

Methods: The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations.

Activation of cholinergic receptors blocks non-adrenergic non-cholinergic contractions in the rat urinary bladder.

In the present study, the plasticity of the non-adrenergic non-cholinergic (NANC) response was investigated. Isolated rat bladder strips were electrically stimulated and the evoked contractions were isometrically recorded. The NANC part of the contractions were unmasked by applying 500 nM 4-DAMP, a potent muscarinic antagonist.

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract.

Botulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C).

Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury.

The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either vehicle (saline containing bovine serum albumin) or BoNT-A.

Comparison of cystometric methods in female rats.

Aims: Rat cystometry is a common model used to investigate urinary storage and voiding function. The effect of cystometric instrumentation in rat studies might be a source of deviation from normal physiologic responses. We hypothesized that transurethral catheterization would produce obstruction-related changes, and that suprapubic catheterization would limit volume-related functions as well as disrupt normal urothelial sensory function.

Is abdominal wall contraction important for normal voiding in the female rat?

Background: Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR) to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding.

Using caveolin-1 knockout mouse to study impaired detrusor contractility and disrupted muscarinic activity in the aging bladder.

Objectives: The caveolin-1 knockout mouse has been proposed as an animal model to study impaired bladder contractility and detrusor overactivity. This study investigated the effects of aging on detrusor contraction in wild type and caveolin-1 knockout mice.

Methods: Young (3-month-old) and old (1-year-old) male caveolin-1 knockout mice and their age-matched male wild type littermates (controls) were used.

The role of the prostacyclin receptor antagonist RO3244019 in treating neurogenic detrusor overactivity after spinal cord injury in rats.

Objective: To determine the effects of the prostacyclin receptor (IP) antagonist RO3244019 on neurogenic detrusor overactivity (NDO) in spinal cord-injured (SCI) neurogenic bladder of the rat.

Materials And Methods: Female Sprague-Dawley rats with SCI were divided into four treatment groups of eight each: vehicle (200 mm Tris base), indomethacin (3 mg/kg), RO3244019 (at 1 and 5 mg/kg). The conscious rats were assessed by cystometry, by slowly infusing the bladder with physiological normal saline at 0.

Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats.

Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T(9)-T(10) level 2-3 weeks prior to the experiment and a microdialysis fiber was inserted in the L(6)-S(1) lumbosacral spinal cord one day before the experiments. Mechanically evoked (i.

Botulinum toxin: poisoning the spastic bladder and urethra.

Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine.

Botulinum toxin in urology: evaluation using an evidence-based medicine approach.

Clinical reports documenting the beneficial effects of botulinum toxin (BTX) to treat various lower urinary tract disorders of muscle spasticity (e.g. detrusor hyperreflexia, detrusor sphincter dyssynergia) have led to its expanded application in non-neurogenic conditions such as idiopathic detrusor overactivity, detrusor underactivity and benign prostatic hyperplasia (BPH).

Age-dependence of the spontaneous activity of the rat urinary bladder.

Abnormal mechanical function of the bladder is manifested in a number of ways including higher frequency of involuntary detrusor contractions associated with reduced compliance of the bladder that is responsible for an increase in intraluminal pressure during filling. There are basically two ways to approach experimentally these problems: (1) by studying the neural control of the lower urinary tract function, and (2) by measuring the properties of smooth muscle cells in the bladder wall. Studies on smooth muscle function often do not take the origin of smooth muscle cells into account i.

In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats.

Objectives: To analyze the in vivo effects of botulinum toxin type A (BTX-A) on visceral sensory function in chronic spinal cord-injured (SCI) rats.

Methods: One group of rats underwent spinal cord transection at the T8-T9 level (SCI) and the other group was left untreated. In 21 days, baseline open cystometrography (CMG) was performed.

Enhanced ATP release from rat bladder urothelium during chronic bladder inflammation: effect of botulinum toxin A.

The effects of mechanoreceptor stimulation and subsequent ATP release in cyclophosphamide evoked chronic bladder inflammation was examined to demonstrate: (1) whether inflammation modulates ATP release from bladder urothelium and (2) whether intravesical botulinum toxin A administration inhibits urothelial ATP release, a measure of sensory nerve activation. ATP release was measured from rat bladders in a Ussing chamber, an apparatus that allows one to separately measure resting and mechanoreceptor evoked (e.g.

Botulinum toxin treatment of urethral and bladder dysfunction.

There has been tremendous excitement with the use of botulinum toxin for the treatment of various urethral and bladder dysfunction over the past several years. Botulinum toxin is the most lethal naturally occurring toxin known to humankind. Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this article, we will review the mechanisms underlying the effects of botulinum toxin treatment.

Inhibitory effect of intravesically applied botulinum toxin A in chronic bladder inflammation.

Purpose: We evaluated a putative inhibitory effect of intravesical botulinum toxin A (BTX-A) on afferent pathways in conditions of chronic bladder inflammation.

Materials And Methods: Female Sprague-Dawley rats were divided into 4 groups, namely group 1-saline treated, group 2-BTX-A treated, group 3-cyclophosphamide (CYP) treated and group 4-BTX-A and CYP treated. At the beginning of the treatment period all animals received intravesical protamine sulfate (1%), followed by intravesical BTX-A or saline.

A case for botulinum toxin-A in idiopathic bladder overactivity.

Botulinum toxin (BTX) has been shown to be an effective agent in suppressing detrusor overactivity due to neurogenic causes. Similar to results obtained with traditional agents to treat bladder overactivity (ie, antimuscarinic medications), the use of BTX has been extended to patients with idiopathic detrusor overactivity. This article briefly reviews the use of BTX to treat disorders of detrusor overactivity and, based on early clinical and laboratory results, establishes the case for its use as a therapeutic modality to treat idiopathic detrusor overactivity.

Botulinum toxin a has antinociceptive effects in treating interstitial cystitis.

Objectives: To present clinical evidence with botulinum toxin A (BTX-A) suggesting an antinociceptive role in patients with interstitial cystitis (IC). Intriguing evidence in a somatic pain model has suggested that BTX-A injection may have an antinociceptive effect on both acute and chronic (inflammatory) pain.

Methods: Thirteen female patients (6 in the United States and 7 in Poland) with IC according to the criteria of the National Institute of Diabetes, Digestive and Kidney Disease were included.

Loss of caveolin-1 expression is associated with disruption of muscarinic cholinergic activities in the urinary bladder.

Caveolin-1 (Cav1), a structural protein of caveolae, plays cell- and context-dependent roles in signal transduction pathway regulation. We have generated a knockout mouse homozygous for a null mutation of the Cav1 gene. Cav1 knockout mice exhibited impaired urinary bladder contractions in vivo during cystometry.