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Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord., Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot., Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats., Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle., Materials and Methods: A total of 24 female Sprague-Dawley® rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies., Results: Mean ± SEM bladder weight was 0.97 ± 0.15 gm in controls and 0.53 ± 0.08 gm in cannabinor treated rats (p <0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 ± 0.07 and 0.06 ± 0.02 ml, mean micturition compliance was 0.032 ± 0.006 and 0.069 ± 0.016 ml/cm H(2)O, and mean bladder wall force at the start of flow was 950 ± 280 and 1,647 ± 325 mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma®) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips., Conclusions: In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The combination of muscarinic receptor and alpha(1)-adrenoceptor antagonists is increasingly used for benign prostatic hyperplasia related lower urinary tract symptoms. In addition to the well established peripheral site of action, little is known about the central effects of muscarinic receptor antagonists and muscarinic receptor/alpha(1)-adrenoceptor antagonist combinations on bladder function, partly due to poor brain penetration after systemic administration. We assessed the effects of intrathecal 5-hydroxymethyl tolterodine, an active metabolite of fesoterodine, in obstructed and nonobstructed rats, and of combined intrathecal 5-hydroxymethyl tolterodine/doxazosin in a rat model of partial urethral obstruction., Materials and Methods: We used 80 male Sprague-Dawley rats to test various doses of intrathecal 5-hydroxymethyl tolterodine and/or intrathecal doxazosin on urodynamic parameters. Urodynamic evaluation without anesthesia was done 3 days after bladder and intrathecal catheterization. Two weeks before urodynamics 40 rats underwent partial urethral obstruction., Results: Intrathecal 5-hydroxymethyl tolterodine had no urodynamic effects in nonobstructed rats. Compared to controls obstructed rats had increased bladder pressure and weight, and voiding frequency. In obstructed rats 5-hydroxymethyl tolterodine restored urodynamic parameters to those seen in nonobstructed animals. Doxazosin had effects similar to those of intrathecal 5-hydroxymethyl tolterodine. When the 2 drugs were combined, at the doses used only small additional effects were observed., Conclusions: Urodynamic changes in obstructed rats can be normalized by intrathecal 5-hydroxymethyl tolterodine and by intrathecal doxazosin. The central pathways on which the 2 drugs act seem to be up-regulated with partial urethral obstruction and less relevant under normal conditions., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia., Materials and Methods: Of the original 36 patients assigned to treatment with 5 mg. finasteride daily (group 1) or placebo (group 2) for 6 months 27 completed an open extension study of 5 mg. finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months and 4.5 years., Results: The treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms., Conclusions: Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long-lasting.

Beta-adrenergic activity of the proximal urethra was studied in 11 patients. Maximum urethral pressure was recorded before, and 20 and 60 minutes after the intravenous administration of 0.5 mg. orciprenaline sulfate. There was a 40 per cent or more decrease in the maximum urethral pressure in 6 of the 11 patients. Beta-adrenoreceptor agonists could prove useful in facilitating vesical emptying by reducing urethral resistance in patients with neurogenic bladder dysfunction.