Bladder instillation of “naked” hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo

Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice

“…Bladder function was evaluated by the following urodynamic parameters: (1) bladder capacity (BC), the volume of infused saline at micturition; (2) basal pressure (BP), the lowest bladder pressure recorded during cystometry; (3) threshold pressure (TP), the bladder pressure immediately before micturition; (4) micturition pressure (MP), the peak bladder pressure during micturition; (5) micturition volume (MV), the volume of urine discharged during micturition; (6) residual volume, 24 the volume of infused saline minus the micturition volume; (7) intermicturition pressure (IMP), the mean pressure between micturitions; (8) spontaneous activity (SA), an approximate index of spontaneous bladder contractions between micturitions (i.e., detrusor overactivity); SA was calculated by subtracting the BP from the IMP. Note that this parameter is identical to that previously described as mean intermicturition oscillatory pressure (MIOP = IP – BP); 21 (9) bladder compliance (B Com ), the change in pressure between voiding contractions, and (10) micturition frequency.…”

“…10,21 Briefly, control and KO mice were anesthetized via intraperitoneal injections of xylazine (7–14 mg/kg) and ketamine (37.5–75 mg/kg) formulated for animal use. The ventral abdominal wall, perineum and upper back were shaved with an electrical shaver and cleansed with povidone–iodine.…”

“…10,21–23 Three days after bladder catheter implantation conscious mice were placed in a mouse metabolic cage and the bladder catheter was connected to a two-way valve connected to a pressure transducer and infusion pump. The pressure transducer was connected via an ETH 400 (CB Sciences, Dover, New Hampshire) transducer amplifier to a MacLab/8e (Analog Digital Instruments, Castle Hill, New South Wales, Australia) data acquisition board.…”

Evaluating the safety and potential activity of URO‐902 (hMaxi‐K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non‐neurogenic) overactive bladder syndrome and detrusor overactivity from two double‐blind, imbalanced, placebo‐controlled randomized phase 1 trials

“…URO‐902 may represent a localized gene therapy approach to treating a benign bladder condition of OAB/urgency incontinence. Instillation of vectors designed to overexpress the BK channel significantly decreases hypercontractility of the bladder of rat models, and preclinical studies have shown that the tissue overexpression lasts for up to 6 months . Modulating the expression levels of BK channels with URO‐902 may possibly treat OAB/DO by reducing the excitability of the detrusor smooth‐muscle.…”

Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction

“…First, recent in vitro findings indicate that hyperpolarization of the detrusor muscle cell membrane via selective activation of the BK Ca channel with a new class of BK Ca channel openers can elicit relaxation of detrusor muscle strips (Turner et al ., 2003). In addition, overexpression of the pore forming subunit of the BK Ca using naked DNA gene transfer techniques was shown to improve bladder hyperactivity in rats with detrusor overactivity due to partial urethral outlet obstruction (Christ et al ., 2001). More specifically, intravesicular injection of hSlo cDNA (coding for the α‐subunit of the human BK Ca channel) virtually eliminated the obstruction‐associated detrusor overactivity.…”