Department of Urology, Fukushima Medical University, Fukushima, Japan.
Int J Urol. 2012 May;19(5):457-64. doi: 10.1111/j.1442-2042.2012.02965.x. Epub 2012 Feb 9.
To determine whether long-term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders.
Male Sprague-Dawley rats underwent surgery to produce bladder outlet obstruction (bladder outlet obstruction group; n = 32) or sham surgery (sham group; n = 16). A total of 2 weeks later, 16 bladder outlet obstruction-rats were given the AT1 antagonist, candesartan, subcutaneously (candesartan group) using an osmotic pump for 4 weeks; the remaining bladder outlet obstruction-rats received vehicle (bladder outlet obstruction group). A total of 6 weeks after surgery, we compared continuous cystometry, bladder weight, strip contraction, histology and messenger ribonucleic acid expression of growth factors, nicotinamide adenine dinucleotide phosphate oxidase 1 and renin-angiotensin system components among the three groups.
Bladder weights markedly increased with bladder outlet obstruction (578 ± 159 mg), and candesartan (344 ± 111 mg) suppressed this increase. Micturition pressure, which was significantly higher with bladder outlet obstruction, was unaffected by candesartan. The shortened micturition interval and decreased micturition volume with bladder outlet obstruction were significantly prolonged and increased by candesartan. Candesartan also significantly decreased residual urine. Histologically, the collagen fiber-to-muscle ratio was significantly increased with bladder outlet obstruction (0.85 ± 0.25) compared with the sham group (0.53 ± 0.18); this increase was suppressed by candesartan (0.49 ± 0.21). The messenger ribonucleic acid expression of heparin-binding epidermal growth factor-like growth factor, transforming growth factor-β1 and nicotinamide adenine dinucleotide phosphate oxidase 1 significantly increased with bladder outlet obstruction, but it was significantly reduced by candesartan. Compared with the bladder outlet obstruction group, candesartan increased the maximal contraction of bladder strips for all stimuli except for angiotensin II.
These findings suggest that bladder angiotensin II type 1 receptors contribute to the pathophysiology of remodeling and dysfunction in obstructed bladder.
确定血管紧张素 II 型 1 型受体拮抗剂的长期给药是否能改善梗阻性膀胱的形态和功能。
雄性 Sprague-Dawley 大鼠接受手术造成膀胱出口梗阻（膀胱出口梗阻组；n = 32）或假手术（假手术组；n = 16）。2 周后，16 只膀胱出口梗阻大鼠使用渗透泵皮下给予血管紧张素 II 型 1 型受体拮抗剂坎地沙坦（坎地沙坦组）4 周；其余膀胱出口梗阻大鼠给予载体（膀胱出口梗阻组）。手术后 6 周，我们比较三组连续测压、膀胱重量、条带收缩、组织学和生长因子、烟酰胺腺嘌呤二核苷酸磷酸氧化酶 1 和肾素-血管紧张素系统成分的信使核糖核酸表达。
膀胱重量显著增加（578 ± 159 mg），坎地沙坦（344 ± 111 mg）抑制了这种增加。梗阻性膀胱导致的排尿压力显著升高，坎地沙坦对此无影响。梗阻性膀胱导致的排尿间隔缩短和排尿量减少，经坎地沙坦处理后显著延长和增加。坎地沙坦还显著减少残余尿量。组织学上，与假手术组（0.53 ± 0.18）相比，膀胱出口梗阻组（0.85 ± 0.25）胶原纤维与肌肉的比例显著增加；坎地沙坦抑制了这种增加（0.49 ± 0.21）。肝素结合表皮生长因子样生长因子、转化生长因子-β1 和烟酰胺腺嘌呤二核苷酸磷酸氧化酶 1 的信使核糖核酸表达在膀胱出口梗阻时显著增加，但坎地沙坦显著降低了它。与膀胱出口梗阻组相比，坎地沙坦增加了除血管紧张素 II 以外的所有刺激的膀胱条带最大收缩。
这些发现表明，膀胱血管紧张素 II 型 1 型受体参与了梗阻性膀胱重塑和功能障碍的病理生理学过程。
