ha-1100 and Urinary-Bladder--Overactive

The objective of the present study was to evaluate anti-inflammatory effects of hydroxyfasudil in a protamine sulfate (PS) induced cystitis rat model. Additionally, we investigated prevention of bladder overactivity (BO), and tissue damage in these experiments.. Animals were divided into four groups. In Groups 1 and 2, chemical induced cystitis model was created by administrating intravesical PS with PE50 catheter by the transurethral route. In Group 1, Rho-kinase inhibitor hydroxyfasudil was administered intaperitoneally, and in Group 2, subjects were administered a corresponding volume of saline in the same way. In Group 3, vehicle was administered intravesically and hydroxyfasudil was administrated intraperitoneally. Group 4 was a control Group, and the vehicle was administered intravesically and intraperitoneally. Micturition frequencies were recorded. Biochemical analyses were performed for oxidative stress, and pathological evaluations were investigated. In vitro contractions of bladder tissue strips were measured in tissue-bath.. There were significantly lower Lipid peroxidase levels and higher levels of Glutathione in Group 1 than Group 2 (P = 0.016, P = 0.001, respectively). There was generally more inflammation in Group 2 than the other groups as determined by microscopy. There were significantly higher frequencies of micturition, lower volume, and mean voided maximum urine output after PS administration in Groups 1 and 2. In vitro contraction responses of bladder strips to potassium chloride and acetylcholine were statistically higher in Group 2 than Groups 1 and 3.. Significant reduction of inflammation by affecting the anti-oxidant defense systems was provided by hydroxyfasudil. Decreased in vitro responses to contractions of bladder smooth muscle strips were obtained. Hydroxyfasudil may be a potential new therapeutic option for inflammation and BO, in rat bladder.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Anti-Inflammatory Agents; Cystitis; Female; Injections, Intraperitoneal; Protamines; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; Treatment Outcome; Urinary Bladder, Overactive

To investigate the effects of the rho-kinase inhibitor hydroxyfasudil on bladder overactivity in cyclophosphamide (CYP)-induced cystitis.. Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg). Four days later, bladder function was evaluated by: (i) monitoring micturition behavior in metabolic cages between hydroxyfasudil- and vehicle-treated animals; (ii) measuring changes in continuous cystometrograms in response to intravenous hydroxyfasudil under anesthesia; and (iii) conducting a functional study examining the effect of hydroxyfasudil on the concentration-response curves to carbachol in bladder tissue strips.. Intraperitoneal injection of hydroxyfasudil (10 mg/kg) significantly increased both the average and maximal voided volumes. Hydroxyfasudil significantly decreased the maximal detrusor pressure, whereas the intercontraction interval was not significantly affected. After administration of 0.1, 0.3, 1, and 3 microM hydroxyfasudil, the maximal contraction of the concentration-response curves to carbachol was significantly reduced to 74.5 +/- 4.2%, 55.2 +/- 5.6%, 29.4 +/- 5.6%, and 21.6 +/- 8.2% of the control values, respectively.. The present findings indicate that hydroxyfasudil might be a new treatment option for CYP-induced detrusor overactivity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Disease Models, Animal; Female; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; Urinary Bladder, Overactive