Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats
Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats
复制标题
氯沙坦对老年性严重高血压大鼠膀胱功能障碍的影响
DOI：
10.1016/j.ejphar.2022.174911
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发表时间：
2022
期刊：
影响因子：
5
通讯作者：
Saito M
中科院分区：
文献类型：
--
作者：
Shimizu S;Nagao Y;Kurabayashi A;Shimizu T;Higashi Y;Karashima T;Saito M
衰老是膀胱功能障碍的主要危险因素。据报道，抗高血压药物血管紧张素II型1受体阻滞剂（ARBs）可以改善啮齿动物模型和人类的下尿路功能障碍。我们的目的是研究一种ARB，氯沙坦，对由衰老相关的严重高血压引起的膀胱功能障碍的预防作用。雄性自发性高血压大鼠（SHRs）（36周龄）给予氯沙坦（0、3或10 mg/kg， p.o.） 18周。以年龄匹配、给药的Wistar Kyoto大鼠（WKYs）作为对照。治疗后测量膀胱、肾脏重量、平均血压、排尿参数。此外，用苏木精和伊红染色评估逼尿肌厚度和膀胱动脉壁厚度。采用周期性酸-希夫染色评估肾脏形态。与WKYs相比，SHRs表现出更高的膀胱重量/体重比（BBR）、肾重量/体重比、平均血压、逼尿肌厚度、膀胱动脉壁厚度、尿量、饮水量、排尿后剩余尿量、膀胱容量、收缩间期、肾小球和肾小管损伤率以及更低的尿渗透压。低剂量氯沙坦降低了shr患者的尿量、排尿后残余尿量和膀胱容量，但并不意味着shr患者的血压。高剂量氯沙坦可降低SHRs患者的BBR、平均血压、逼尿肌厚度、膀胱动脉壁厚度、排尿后残余尿量、膀胱容量、收缩间期以及肾小球和肾小管损伤。氯沙坦抑制老年shr患者膀胱功能障碍。ARB氯沙坦可能是一种预防老年高血压引起的膀胱功能障碍的药物。
Aging is a major risk factor for bladder dysfunction. Anti-hypertensive drugs, angiotensin II type 1 receptor blockers (ARBs), are reported to ameliorate lower urinary tract dysfunction in rodent models and humans. We aimed to examine the preventive effect of an ARB, losartan, against bladder dysfunction due to aging-related severe hypertension. Male spontaneously hypertensive rats (SHRs) (36-week-old) were administered losartan (0, 3, or 10 mg/kg, p.o.) for 18 weeks. Age-matched, vehicle-treated Wistar Kyoto rats (WKYs) were used as controls. After the treatments, bladder and renal weight, mean blood pressure, and voiding parameters were measured. Additionally, detrusor thickness and bladder arterial wall thickness were evaluated using hematoxylin and eosin staining. Renal morphology was also assessed using periodic acid-Schiff staining. Compared to WKYs, SHRs demonstrated significantly higher bladder weight/body weight ratio (BBR), renal weight/body weight ratio, mean blood pressure, detrusor thickness, bladder arterial wall thickness, urine output, water intake, post-voiding residual urine volume, bladder capacity, intercontraction interval, and rate of glomerular and tubular injury and a lower urine osmolality. A low dose of losartan decreased the urine output, post-voiding residual urine volume, and bladder capacity in SHRs but not mean blood pressure in SHRs. A high dose of losartan decreased the BBR, mean blood pressure, detrusor thickness, bladder arterial wall thickness, post-voiding residual urine volume, bladder capacity, intercontraction interval, and glomerular and tubular injury in SHRs. Losartan inhibits bladder dysfunction in aged SHRs. The ARB losartan might be a preventive drug for bladder dysfunction due to aging-related severe hypertension.