Abstract

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.

Links

Publisher Full Text

Authors

Gratzke C, Streng T, Stief CG, Alroy I, Limberg BJ, Downs TR, Rosenbaum JS, Hedlund P, Andersson KE

Institution

Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund, Sweden.

Source

The Journal of urology 185:2 2011 Feb pg 731-6

MeSH

Animals
Cannabinol
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Injections, Intraperitoneal
Muscle Contraction
Muscle, Smooth
Random Allocation
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB2
Reference Values
Treatment Outcome
Urethral Obstruction
Urinary Bladder
Urinary Bladder Diseases
Urination

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21168864