Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund, Sweden.
J Urol. 2011 Feb;185(2):731-6. doi: 10.1016/j.juro.2010.09.080. Epub 2010 Dec 18.
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.
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.
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.
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.
我们研究了新型选择性大麻素 2 受体激动剂大麻隆（Procter & Gamble Pharmaceuticals，俄亥俄州辛辛那提）对慢性治疗的影响，该药物对部分尿道梗阻的清醒大鼠的膀胱功能和分离的逼尿肌功能特性的影响。
总共 24 只接受过手术部分尿道梗阻的雌性 Sprague-Dawley®大鼠每天接受腹腔内注射 3mg/kg 大麻隆（12 只）或生理盐水作为对照（12 只），持续 2 周。进行膀胱测压，处死大鼠并准备用于离体研究。
对照组平均±SEM 膀胱重量为 0.97±0.15g，大麻隆治疗组为 0.53±0.08g（p<0.05）。两组间平均排尿间隔或平均基础、阈值、流量或最大压力无差异。在对照组和大麻隆治疗组中，平均残余尿量分别为 0.28±0.07 和 0.06±0.02ml，平均排尿顺应性分别为 0.032±0.006 和 0.069±0.016ml/cmH2O，起始流量时膀胱壁力分别为 950±280 和 1647±325mN/gm（p<0.05）。非排尿收缩在大麻隆治疗组中明显比对照组中少。我们注意到两组间卡巴胆碱（Sigma®）半最大浓度无差异，但大麻隆治疗组的逼尿肌条的卡巴胆碱最大反应明显高于对照组。
在接受大麻隆治疗 14 天的部分尿道梗阻大鼠中，与对照组相比，膀胱重量较低，排空膀胱的能力得到保留，非排尿收缩频率较低。与对照组相比，来自大麻隆治疗组的逼尿肌制剂对神经刺激的反应更高。选择性大麻素 2 受体激活可能是一种新的原则，可在部分尿道梗阻后改善膀胱功能。
