Involvement of angiotensin II type 1 receptor on pathological remodeling and dysfunction in obstructed bladder
Involvement of angiotensin II type 1 receptor on pathological remodeling and dysfunction in obstructed bladder
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DOI：
10.1111/j.1442-2042.2012.02965.x
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发表时间：
2012-05-01
影响因子：
2.6
通讯作者：
Yamaguchi, Osamu
中科院分区：
文献类型：
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作者：
Aikawa, Ken;Sakai, Takio;Yamaguchi, Osamu
目的：探讨长期应用血管紧张素II 1型受体拮抗剂是否能改善梗阻性膀胱的形态和功能。方法：雄性SD大鼠行手术造成膀胱出口梗阻(膀胱口梗阻组，n=32)或假手术(Sham组，n=16)。共2周后，16只膀胱出口梗阻大鼠用渗透压泵皮下注射血管紧张素转换酶1拮抗剂坎地沙坦(坎地沙坦组)，持续4周；其余膀胱出口梗阻大鼠(膀胱出口梗阻组)接受赋形剂治疗。结果：膀胱出口梗阻(578+/-159 mg)组大鼠膀胱重量明显增加(P<0.05)，坎地沙坦(344+/-111 mg)抑制了上述变化。排尿压力在膀胱出口梗阻时显著升高，坎地沙坦对其无影响。坎地沙坦可显著延长和增加膀胱出口梗阻患者排尿间期缩短和尿量减少。坎地沙坦还显著减少了残余尿量。组织学上，膀胱出口梗阻后胶原纤维/肌肉比值(0.85+/-0.25)显著高于假手术组(0.53+/-0.18)；坎地沙坦(0.49+/-0.21)可抑制这一增加。肝素结合的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，坎地沙坦则显著降低。与膀胱出口梗阻组相比，坎地沙坦对除血管紧张素II外的所有刺激均能增加膀胱条的最大收缩。结论：膀胱血管紧张素II 1型受体参与了梗阻性膀胱重塑和功能障碍的病理生理过程。
Objectives: To determine whether long-term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders.Methods: 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.Results: 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-beta 1 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.Conclusion: These findings suggest that bladder angiotensin II type 1 receptors contribute to the pathophysiology of remodeling and dysfunction in obstructed bladder.