retinol-acetate and Urinary-Bladder--Overactive

In overactive bladder (OAB) therapy several herbal medicines presented promising effects, however the results are sparse to provide their efficacy. Herbals may become a popular alternative for OAB therapy. Therefore, we investigated whether Potentilla chinensis extract (PCE) would reverse retinyl acetate (RA)-induced detrusor overactivity (DO).. 60 rats were divided into 4 groups, as follows: I - control, II - rats with RA-induced DO, III - rats received PCE in dose of 500 mg/kg, and IV - rats with RA-induced DO which received PCE. PCE or vehicle were administered orally for 14 days. The cystometry and bladder blood flow assessment were performed 3 days after the last dose of the PCE. Then the rats were put into the metabolic cages for 24 h. Next, urothelium thickness measurement and biochemical analyses were performed. < /p>

Results. Intravesical infusion of RA solution induced DO. PCE had no influence on the urinary bladder function and  micturition cycles in normal rats. PCE diminished the severity of RA-induced DO. In the urothelium the RA induced the elevation of ATP, CGRP, substance P, VEGF-A, OTC3, and ERK1/2. The concentration of NOS2, CDH1, and ZO1 decreased. Moreover, RA affected the concentration of SNARE proteins (increased concentration of SNAP23, SNAP25, and SV2A). Also in detrusor the elevated level of ROCK1 and VAChT were observed. In turn, PCE in RA-induced DO caused a reversal of the described biochemical changes within urothelium, detrusor muscle and urine. < /p>

Conclusions. PCE attenuates detrusor overactivity. The potential mechanisms of action of PCE in the urinary bladder seem to be multifactorial and complex. PCE seems to become a reasonable novel OAB therapy.

Topics: Animals; Disease Models, Animal; Diterpenes; Female; Plant Extracts; Potentilla; Rats; Rats, Wistar; Retinyl Esters; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination

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.

Topics: Administration, Intravesical; Animals; Disease Models, Animal; Diterpenes; Female; Heterocyclic Compounds, 4 or More Rings; Rats, Wistar; Retinyl Esters; Urinary Bladder, Overactive; Urination; Urodynamics; Vitamin A

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.

Topics: Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Antagonists; Animals; Arterial Pressure; Blood Pressure; Diterpenes; Diuresis; Ethanolamines; Female; Heart Rate; Infusions, Intra-Arterial; Nebivolol; Rats; Rats, Wistar; Retinyl Esters; Urinary Bladder, Overactive; Urodynamics; Vitamin A