Detrusor Overactivity Index Research Articles

New Kid on the Block: The Efficacy of Phytomedicine Extracts Urox® in Reducing Overactive Bladder Symptoms in Rats.

The aim of the current study was to determine if phytomedicine (Urox®) would reverse retinyl acetate (RA)–induced changes characteristic of bladder overactivity. There were 60 rats divided into the following 4 groups: I—control, II—received RA to induce detrusor overactivity (DO), III—received Urox (840 mg daily for 14 days), and IV—received combination of RA and Urox®. The cystometry was performed 2 days after the last dose of Urox®. Next, urothelium thickness and biochemical parameter measurements were performed. In group IV, a decrease in basal pressure and detrusor overactivity index was noted when compared to group II. Furthermore, in group IV the following parameters were increased: threshold pressure, voided volume, intercontraction interval, and bladder compliance in comparison with group II. There were significant elevations in c-Fos expression in the neuronal voiding centers in group II, while the expression of c-Fos in group IV was normalized. No significant changes in the values of the analyzed biomarkers in group III were found, while in group II, an elevation in BDNF, NGF, CGRP, ATP, Rho kinase, malondialdehyde, 3-nitrotyrosine, TRPV1, OCT-3, and VAChT and then a decrease in E-cadherin and Z01 were found. A successful restoration of all the abovementioned biomarkers’ levels was observed in group IV. Phytomedicine extracts (Urox®) were found to be potent in reversing RA-induced changes in several cystometric and biochemical parameters that are determinants of overactive bladder (OAB). The actions of Urox® were proved to be dependent on several factors, such as growth factors and several OAB biomarkers but not pro-inflammatory cytokines.

Detrusor overactivity assessment using ultrasound bladder vibrometry

Objective. Detrusor overactivity (DO) is a urodynamic observation characterized by fluctuations in detrusor pressure (P det) of the bladder. Although detecting DO is important for the management of bladder symptoms, the invasive nature of urodynamic studies (UDS) makes it a source of discomfort and morbidity for patients. Ultrasound bladder vibrometry (UBV) could provide a direct and noninvasive means of detecting DO, due to its sensitivity to changes in elasticity and load in the bladder wall. In this study, we investigated the feasibility and applying UBV toward detecting DO. Approach. UBV and urodynamic study (UDS) measurements were collected in 76 neurogenic bladder patients (23 with DO). Timestamped group velocity squared () data series were collected from UBV measurements. Concurrent P det data series were identically analyzed for comparison and validation. A processing approach is developed to separate transient fluctuations in the data series from the larger trend of the data and a DO index is proposed for characterizing the transient peaks observed in the data. Main Results. Applying the DO index as a classifier for DO produced sensitivities and specificities of 0.70 and 0.75 for data series and 0.70 and 0.83 for P det data series respectively. Significance. It was found that DO can be feasibly detected from data series of timestamped UBV measurements. Collectively, these initial results are promising, and further refinement to the UBV measurement process is likely to improve and clarify its capabilities for noninvasive detection of DO.

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T–H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

The effect of O-1602, a GPR55 agonist, on the cyclophosphamide-induced rat hemorrhagic cystitis

The goal of our study was to determine whether GPR55 agonists, O-1602, could reverse the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters, indicative of the development of bladder inflammation and overactivity. If confirmed, the stimulation of novel cannabinoid receptor - GPR55, could be a reasonable strategy as a treatment of CYP-induced haemorrhagic cystitis. The experiments were conducted in female Wistar rats. Based on the methodology of our published studies on CYP-induced heamorrhagic cystitis we performed experiments after administration of CYP, O-1602 or CYP plus O-1602. These included surgical procedures, conscious cystometry, measurements of bladder oedema and urothelium thickness using the Evans Blue dye leakage technique, as well as biochemical analyses with particular ELISA kits. O-1602 ameliorated the symptoms of CYP-induced detrusor overactivity leading to an increase in voided volume (0.59 vs. 0.93ml), and lowering the detrusor overactivity index (703 vs. 115cm H2O/ml). Intravenous administration of the GPR55 agonist to animals that received CYP significantly decreased Evans Blue extravasation and increased urothelium thickness. O-1602 also reversed the pro-inflammatory activity of CYP by restoring concentrations of brain-derived neurotrophic factor, nerve growth factor, calcitonin gene related peptide, interleukin 1-beta, interleukin-6, tumour necrosis factor alpha, malondialdehyde, nitrotyrosine, occludin, and organic cation transporter 3. GPR55 agonist, O-1602, represents a novel class of uroprotective agents, targeting the inflammatory basis of cystitis. To our knowledge, this is the first paper proposing O-1602 agent, as a candidate for future studies in the treatment of CYP-induced cystitis.

The influence of nebivolol on the activity of BRL 37344- the β3-adrenergic receptor agonist, in the animal model of detrusor overactivity.

The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol(NEB) on the activity of BRL 37344-β3-adrenergic receptor (β3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. Retinyl acetate (RA;0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. β3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the β3AR agonist. The combined application of the β3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.

Blebbistatin reveals beneficial effects on the cystometric parameters in an animal model of detrusor overactivity

The aims of the study were to determine the effectiveness of blebbistatin (BLEB) on detrusor overactivity (DO) in an animal model induced by retinyl acetate (RA) and, because of potential urothelial permeability, to evaluate the degenerative impact of BLEB on the urothelium. Three days after RA instillation into the urinary bladder, BLEB was administered into the bladder and immediately after cystometric assessment was performed. Furthermore, Evans Blue extravasation into bladder tissue and urothelium thickness were measured. Sixty female Wistar rats were used and randomly assigned to one of four groups (n = 15 in each group): (1) control, (2) RA, (3) BLEB, and (4) RA + BLEB. RA administration induced changes in cystometric parameters reflecting DO, as previously reported. Treatment with BLEB did not significantly alter cystometric parameters in rats which did not receive RA. Administration of BLEB to rats pretreated with RA reversed changes in cystometric parameters induced by RA in basal pressure, threshold pressure, detrusor overactivity index, amplitude of nonvoiding contractions, frequency of nonvoiding contractions, voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. There were no significant differences in Evans Blue extravasation into bladder tissue or urothelium thickness between the groups. The current research provides new data on the possible utility of blebbistatin in the pharmacotherapy of DO, which is an important feature of overactive bladder (OAB). Further studies in human patients with DO/OAB are warranted to confirm these preclinical results.

The angiotensin II receptors type 1 blockage affects the urinary bladder activity in hyperosmolar-induced detrusor overactivity in rats: Preliminary results.

Angiotensin II receptors play a role in the pathogenesis of urinary bladder dysfunction, especially in the case of bladder outlet obstruction. The function of these receptors in the detrusor overactivity (DO) still remains unclear. The study aims to investigate some of the mechanisms through which hyperosmolarity induces urinary bladder overactivity. The effect of angiotensin II receptor type 1 - AT1 (telmisartan) on urinary bladder function in physiological state and in hyperosmolar-induced DO in rat model was explored. Experiments were performed on 32 female Wistar rats. DO was induced by hyperosmolar saline intravesical instillation. Surgical procedures and cystometry were performed under urethane anesthesia. The measurements represent the average of 5 bladder micturition cycles. We analyzed: basal pressure, threshold pressure, micturition voiding pressure, intercontraction interval, compliance, functional bladder capacity, motility index and detrusor overactivity index. Intravesical hyperosmolar saline instillation induced DO. Telmisartan diminished the severity of hyperosmolar-induced DO. We observed a statistically significant increase of intercontraction interval (55%), functional bladder capacity (54%), compliance (140%). Also, a statistically significant decrease of detrusor overactivity index (18%) and motility index (9%) were observed. The difference of basal pressure, threshold pressure and micturition voiding pressure were not statistically significant. Moreover, telmisartan has no effect on urodynamic parameters in naïve rats. Detrusor overactivity due to intravesical increased osmolarity seems to be at least partially mediated by AT1 receptors activity. On one hand, telmisartan diminished the severity of hyperosmolarinduced DO, and, on the other hand, has no effect on urodynamic parameters in naïve rats.

The influence of duloxetine on detrusor overactivity in rats with depression induced by 13-cis-retinoic acid

Introduction and hypothesisThe aim of this study was to assess the efficacy of duloxetine in an animal model of detrusor overactivity induced by depression.MethodsAfter 6 weeks of 13-cis-retinoic acid administration at a dose of 1 mg/kg/day, rats were given duloxetine at a dose of 1 mg/kg. This was followed by conscious cystometry, a forced swim test, and locomotor activity measurement. The levels of corticotropin-releasing factor (CRF) in the hypothalamus, amygdala and plasma were also determined.ResultsDuloxetine treatment led to a reduction in detrusor overactivity symptoms induced by the retinoid. Decreases were observed in cystometric parameters including the detrusor overactivity index, and the amplitude and frequency of nonvoiding contractions, while increases were seen in bladder compliance and the volume threshold to elicit nonvoiding contractions. No statistically significant differences were found in basal pressure, threshold pressure, micturition voiding pressure, postvoid residual , volume threshold, voiding efficiency, intercontraction interval, bladder contraction duration or relaxation time. Duloxetine also reduced the immobility time to that observed in control animals, while it did not affect locomotor activity. Its effects also included lowering of the CRF levels in the hypothalamus, amygdala and plasma, which increased following the prior administration of the retinoid. The plasma level of 13-cis-retinoic acid in rats corresponded to the levels found in humans.ConclusionsThis is the first study showing the efficacy of duloxetine in an animal model of detrusor overactivity induced by depression. Further studies in patients with detrusor overactivity and coexisting depression are warranted to confirm these experimental results.

Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats

Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors may suppress detrusor overactivity symptoms and possess anti-inflammatory properties. The aim of the present study was to investigate whether inhibition of ROCK reduces cystometric and histopathological changes associated with CYP-induced cystitis. The rats received GSK 269962, a ROCK inhibitor, at a dose of 30 mg/kg daily, or vehicle for 7 days. Then, acute chemical cystitis leading to bladder overactivity was induced by CYP injection (200 mg/kg i.p.). Following CYP injection, cystometric studies with physiological saline were performed. Moreover, bladder edema (by the Evans Blue dye leakage technique) and urothelium thickness were measured. CYP injection resulted in a significant increase in cystometric parameters: basal pressure, threshold pressure, bladder contraction duration, relaxation time, detrusor overactivity index, non-voiding contractions amplitude, and non-voiding contractions frequency as well as increased Evans Blue extravasation into bladder tissue, whereas micturition voiding pressure, voided volume, post-void residual, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit non-voiding contractions as well as urothelium thickness were significantly decreased in CYP-injected rats. Administration of GSK 269962 normalized the abovementioned CYP injection-induced changes. Inhibition of ROCK was found to ameliorate CYP-induced detrusor overactivity and bladder inflammation. Our data indicate uroprotective effects following ROCK inhibition, which further suggests that this strategy may become an interesting pharmacological tool to prevent urinary adverse effects in patients treated with chemotherapy using CYP.

The Influence of Maxacalcitol, Vitamin D3 Analog, on Detrusor Overactivity in Conscious Rats

To test the hypothesis that maxacalcitol, vitamin D3 analog, would ameliorate detrusor overactivity (DO) induced by retinyl acetate instillation; to test the outcome of the combined administration of maxacalcitol and the rho kinase inhibitor - GSK 269962, amlodipine besylate, or oxybutynin chloride in this model. The rats were treated with maxacalcitol for 14 days. Then, cystometric studies were performed during which the animals were administered test compounds. Maxacalcitol in a dose of 30 but not 15 µg/kg/day induced reduction in DO index, non-voiding contractions frequency (FNVC), and amplitude (ANVC), while increasing volume threshold to elicit non-voiding contractions (VTNVC). The 14-day-long administration of maxacalcitol at a dose of 15 µg/kg/day to animals, followed by GSK 269962 at a single dose of 10 mg/kg, led to a statistically significant reduction of intercontraction interval and bladder compliance, and an increase in DO index, without any effect on ANVC, FNVC, and VTNVC. The assessment of the combined effect of maxacalcitol (15 µg/kg/day) and amlodipine besylate (0.25 mg/kg) demonstrated an increase in intercontraction interval, bladder compliance and VTNVC, with a decrease in FNVC. No statistically significant changes were found in DO index and ANVC. The combined outcome of administering maxacalcitol (15 µg/kg/day) and oxybutynin chloride (0.25 mg/kg) did not show any statistically significant value of the measured cystometric parameters. The outcomes of maxacalcitol administration can be the result of 3 mechanisms, that is, the upregulation of L-type Ca(2+) channels, the inhibition of the rho kinase pathway, and a so far unknown central mechanism.

Ovariectomy May Induce Detrusor Overactivity in Rats: The Therapeutic Role of Rho Kinase Inhibition

To verify the impact of ovariectomy (OVX) on the micturition cycle in conscious rats; to examine the influence of rho kinase (ROCK) inhibition on the bladder detrusor in OVX rats; to assess the effect of the joint administration of the ROCK inhibitor (GSK 269962) and solifenacin succinate (SOL) to these animals. The impact of OVX or a single dose of GSK 269962 and/or SOL on the cystometric parameters was assessed 28 days after the procedure. OVX caused an increase in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions, along with a decrease in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. GSK 269962 administered in a dose of 10 mg/kg (but not 5 mg/kg) or SOL in a dose of 0.03 mg/kg (but not 0.015 mg/kg) triggered an increase in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, along with a decrease in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions. A combined administration of GSK 269962 (5 mg/kg) and SOL (0.15 mg/kg), in doses ineffective in monotherapy, triggered a reversal in the OVX-induced cystometric changes. It appears that ROCK inhibitors can become an alternative worth considering in overactive bladder syndrome treatment, especially in the light of the findings pointing to the decreased efficiency of antimuscarinic drugs in the overactive bladder syndrome treatment of postmenopausal women.

The effect of combined treatment with a β3 AR agonist and a ROCK inhibitor on detrusor overactivity.

The objective of the study was to evaluate the efficacy and safety of the combined treatment with the β3 AR agonist and ROCK inhibitor in the rat model of detrusor overactivity induced by retinyl acetate instillation. The ROCK inhibitor (GSK 269962) and/or the β3 AR agonist (BRL 37344) were administered in single doses and a cystometry was carried out, along with a 24 hr measurement of cardiovascular parameters and diuresis. The combined use of GSK 269962 and BRL 37344 in doses ineffective in monotherapies, ameliorated DO. An increase was found in voided volume, voiding efficiency, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, accompanied by a decrease in basal pressure, threshold pressure, detrusor overactivity index, nonvoiding contractions amplitude, and frequency. The combination therapy in question proved to have no effect on micturition voiding pressure, post-void residual, bladder contraction duration, or relaxation time. A 24 hr observation of female rats who received GSK 269962 and/or BRL 37344 did not show any significant changes in urine production. BRL 37344 increased heart rate and blood pressure proportionately to the applied dose. The assessment of the combined treatment with GSK 269962 and BRL 37344 revealed a significant drop of cardiovascular parameters when compared to the rats which only received BRL 37344. The combined use of β3 AR agonists and ROCK inhibitors may improve overactive bladder treatment efficacy and minimize side effects. This polytherapy appears to improve urine storage with no impairment of voiding function. Neurourol. Urodynam. 36:580-588, 2017. © 2016 Wiley Periodicals, Inc.

The influence of Rho-kinase inhibition on acetic acid-induced detrusor overactivity.

Accumulating evidence has shown that Rho-kinase (ROCK) is involved in the regulation of bladder contraction. Our objective was to examine whether the ROCK inhibitor, GSK 269962, could prevent acetic acid (AA)-induced detrusor overactivity and to assess its influence on urine production (UP) and mean arterial pressure (MAP). The bladder was catheterized from the external urethral orifice. 0.25 % (AA) solution was infused into the bladder for 5 min. In the same session a catheter was inserted into the apex of the bladder dome. In order to measure the blood pressure, the carotid artery was cannulated. Three days after the intravesical instillation of AA, the ROCK-GSK 269962 inhibitor was administered in a single dose of 10 mg/kg and a cystometry was carried out, along with a 24 hr measurement of UP and MAP. GSK 269962 reversed the changes induced by AA causing a drop in basal pressure, threshold pressure, micturition voiding pressure, bladder contraction duration, relaxation time, detrusor overactivity index, amplitude, and frequency of nonvoiding contractions while an increase in voided volume, post-void residual, volume threshold, voiding efficiency, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. ROCK inhibition did not show any significant changes in UP and MAP. The results obtained indicate that ROCK inhibition may ameliorate AA-induced bladder overactivity. ROCK inhibitors appear to represent a potentially attractive pharmacological option for the treatment of lower urinary tract disorders associated with changes in detrusor contractility. Neurourol. Urodynam. 36:263-270, 2017. © 2015 Wiley Periodicals, Inc.

A new model of detrusor overactivity in conscious rats induced by retinyl acetate instillation.

A credible animal overactive bladder model used in basic research is an indispensable harbinger of safe and ethical clinical trials on human subjects. Our objective was to develop a new animal model of a hyperactive bladder that will be void of inflammatory urothelium lesions and display significant sensitivity to muscarinic receptor antagonists. To examine the influence of 0.75% retinyl acetate solution on cystometric parameters, it was infused into the bladder for 5min. Cystometric studies with physiological saline were performed in conscious unrestrained rats 3days later. To examine the influence of retinyl acetate, acetic acid or cyclophosphamide on morphology of urinary bladders, the bladders were subjected to histopathological examination. We demonstrated that in rats subject to previous 5-minute bladder instillations with retinyl acetate, an increase of basal pressure, threshold pressure, micturition voiding pressure, bladder contraction duration, relaxation time, detrusor overactivity index, nonvoiding contraction frequency and amplitude occurs. On the other hand, a decrease in voided volume, post-void residual, volume threshold, voiding efficiency, intercontraction interval, bladder compliance and volume threshold to elicit nonvoiding contractions was observed. Administration of oxybutynin chloride (0.5mg/kg, i.v.) reversed changes of cystometric parameters evoked by retinyl acetate. Contrary to acetic acid and cyclophosphamide, bladders subjected to retinyl acetate infusion had no signs of bladder inflammation. The results obtained indicate that transient infusion of 0.75% retinyl acetate can induce detrusor overactivity, which is often observed in patients with overactive bladder syndrome (OAB). In addition, it was demonstrated that stimulating afferent C-fibres using retinyl acetate did not induce evident histopathological inflammatory lesions in the urinary bladder wall. It appears that in the future this model can prove useful in gaining more knowledge on the pathophysiology of OAB, and contribute to the preparation of new, more effective options of OAB pharmacotherapy.

The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats

The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO). We compared urinary bladder activity in response to blockade of CB1 and CB2 receptors using AM281 and AM630, respectively, in normal rats and after hyperosmolar stimulation. Experiments were performed on 44 rats. DO was induced by intravesical instillation of hyperosmolar saline. Surgical procedures and cystometry were performed under urethane anaesthesia. The measurements represent the average of 5 bladder micturition cycles. We analysed basal, threshold, and micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; and detrusor overactivity index. The blockage of CB1 and CB2 receptors diminished the severity of hyperosmolar-induced DO. In comparison with naïve animals the increased frequency of voiding with no significant effect on intravesical voiding pressure profile was observed as a result of the blockage of CB1 and CB2 receptors. These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.

The Ameliorating Effect of Exogenous Melatonin on Urinary Bladder Function in Hyperosmolar Bladder Overactivity and its Influence on the Autonomic Nervous System Activity

This study was designed to investigate the effects of melatonin on the bladder hyperactivity in hyperosmolar-induced overactive bladder (OAB) rats. Additionally, the influence of melatonin on the autonomic nervous system (ANS) using heart rate variability (HRV) analysis was assessed. 40 rats were divided into four groups: I--control (n = 12), II--rats with hyperosmolar OAB (n = 6), III--rats with melatonin pretreatment and hyperosmolar OAB (n = 6) and IV--control with melatonin pretreatment (n = 6). In group III and IV melatonin in dose of 100 mg/kg was given. HRV measurements in 10 rats, as follow: control (n = 2), control after melatonin treatment (n = 2), rats with hyperosmolar OAB without (n = 3), and after (n = 3) melatonin treatment were conducted. This study demonstrates marked influence of melatonin on urinary bladder activity in hyperosmolar-induced OAB rats. These rats showed significantly reduced the detrusor motor overactivity resulting in the improvement of cystometric parameters after melatonin treatment when compared to the control, as follow: a significant increase of intercontraction interval (70%) and functional bladder capacity (67%), as well as a decrease of the basal pressure, detrusor overactivity index and motility index of 96%, 439% and 40%, respectively. ANS activity analysis revealed sympathetic overactivity in OAB rats, and parasympathetic superiority in melatonin treated OAB rats. Melatonin treatment in rats with hyperosmolar OAB (group III) caused significant increase of nuHF parameter (from 51.00 +/- 25.29 to 76.97 +/- 17.43), as well as a decrease of nuLF parameter (from 49.01 +/- 25.26 to 23.03 +/- 17.43) and LF/HF ratio (from 1.280 +/- 0.980 to 0.350 +/- 0.330). In conclusion, melatonin suppresses hyperosmolar OAB, and modulates ANS activity by inhibition of the sympathetic drive. Therefore, melatonin may become a useful agent for OAB management.

Hyperosmolarity alters micturition: a comparison of urinary bladder motor activity in hyperosmolar and cyclophosphamide-induced models of overactive bladder

Hyperosmolar factors induce the neurogenic inflammatory response, leading to bladder overactivity (OAB). The aim of the study was to compare the bladder motor activity in a hyperosmolar and acute cyclophosphamide (CYP)-induced model of OAB. Furthermore, we set our sights on defining the most physiological model of OAB in experimental practice. Forty-two female rats were divided randomly into 5 groups. All animals underwent cystometry with the usage of isotonic saline or saline of increasing concentration. Acute chemical cystitis was induced by CYP to elicit OAB. The following cystometric parameters were analyzed: basal pressure, threshold pressure, micturition voiding pressure, intercontraction interval, compliance, functional bladder capacity, motility index, and detrusor overactivity index. CYP and hypertonic saline solutions induced OAB. Having been compared with CYP OAB, none of the rats infused with hypertonic solution exhibited macroscopic signs of bladder inflammation. The comparison of CYP and hyperosmolar models of OAB revealed that the greatest similarity existed between the 2080 mOsm/L OAB model and the acute CYP-induced model. We postulate that the 2080 mOsm/L model of OAB can be established as being a less invasive and more physiological model when compared with the CYP-induced OAB model. Additionally, it may also be a more reliable experimental tool for evaluating novel therapeutics for OAB as compared with CYP-induced models.