Department of General medicine and Emergency care, Faculty of Medicine, Toho University, Tokyo, Japan.
J Renin Angiotensin Aldosterone Syst. 2011 Jun;12(2):65-74. doi: 10.1177/1470320310387844. Epub 2011 Mar 8.
The nephro-protective effects of angiotensin II receptor blockers (ARBs) are widely known; however, there are few reports of long-term effects focusing on the renal vessels. We studied afferent arteriolar changes induced by the long-term administration of an ARB.
Thirty-two 6-week-old male Zucker fatty rats (ZFRs) were divided into following four groups (n = 8 in each): ZFR Group and ZFR+High Group fed a standard or high-salt diet, respectively; ZFR+ARB Group and ZFR+High+ARB Group fed a standard or high-salt diet with ARB (Olmesartan, 5 mg/kg/day), respectively. Blood pressure, proteinuria, morphological examinations and glomerular haemodynamics in vivo were studied.
Marked proliferative changes in the afferent arteriolar smooth muscle cells (SMCs) were frequently observed in the two groups given ARBs; in the ZFR+ARB group (77.3±10.3%) compared with the two groups without ARB (1.7%, p < 0.005; 1.2%, p < 0.0005) and 37.4±15.6% in the ZFR+High+ARB group. Proteinuria markedly decreased in the groups treated with ARBs, but the glomerular erythrocyte velocities showed no differences.
Our findings indicate that long-term ARB administration induced unusual proliferative changes in SMCs of afferent arterioles of ZFRs. These changes could narrow arteriolar lumens and reduce intraglomerular pressure, but they could cause also irreversible damage to the arterioles.
血管紧张素 II 受体阻滞剂 (ARB) 的肾脏保护作用已广为人知;然而,关于长期作用对肾脏血管的影响的报道很少。我们研究了长期应用 ARB 引起的入球小动脉的变化。
32 只 6 周龄雄性 Zucker 肥胖大鼠 (ZFR) 分为以下四组(每组 n = 8):ZFR 组和 ZFR+高盐组分别给予标准或高盐饮食;ZFR+ARB 组和 ZFR+高盐+ARB 组分别给予标准或高盐饮食加 ARB(奥美沙坦,5mg/kg/天)。研究了血压、蛋白尿、形态学检查和体内肾小球血流动力学。
ARB 组的入球小动脉平滑肌细胞(SMC)增殖明显;与未用 ARB 的两组相比(1.7%,p < 0.005;1.2%,p < 0.0005),ZFR+ARB 组(77.3±10.3%)更为明显;ZFR+高盐+ARB 组为 37.4±15.6%。ARB 治疗组蛋白尿明显减少,但肾小球红细胞速度无差异。
我们的研究结果表明,长期 ARB 治疗可引起 ZFR 入球小动脉 SMC 异常增殖。这些变化可能会缩小小动脉管腔并降低肾小球内压,但也可能对小动脉造成不可逆转的损害。