Institute of Physiology, Univ. of Regensburg, Universitätsstr. 31, 93040 Regensburg, Germany.
Am J Physiol Renal Physiol. 2013 Oct 15;305(8):F1189-200. doi: 10.1152/ajprenal.00377.2013. Epub 2013 Aug 14.
In this study, we assessed the acute effects of angiotensin II on the albumin glomerular sieving coefficient (GSC) using intravital microscopy. The experiments were performed on Munich Wistar Froemter (MWF) rats. Alexa-Fluor-594 albumin was injected intravenously, and the fluorescence intensity in the glomerular capillaries and Bowman's space was determined to calculate the albumin GSC. The GSC was measured before and during the constant infusion of angiotensin II (10 ng·min(-1)·kg(-1) body wt). Baseline mean arterial pressure (MAP) was 99 ± 5 mmHg and stabilized at 137 ± 5 mmHg during angiotensin II infusion. The baseline GSC averaged 0.00044 ± 4.8 × 10(-5) and increased by 286 ± 44% after angiotensin II infusion (P < 0.0001). The proximal tubular Alexa-Fluor-594 albumin uptake was enhanced during angiotensin II infusion (518% of the baseline value during angiotensin II vs. 218% in controls; P < 0.0001). No change in GSC was observed when the AT1 antagonist losartan was injected before the start of angiotensin II infusion. The AT2 antagonist PD123319 increased the baseline GSC from 0.00052 ± 3.6 × 10(-5) to 0.00074 ± 8.2 × 10(-5) (P = 0.02) without altering the MAP. During angiotensin II infusion with losartan, PD123319 increased the albumin GSC from 0.00037 ± 5.8 × 10(-5) to 0.00115 ± 0.00015 (P = 0.001). When the renal perfusion pressure was mechanically controlled, the GSC increased from 0.0007 ± 0.00019 to 0.0025 ± 0.00063 during angiotensin II infusion (P = 0.047), similar to what was observed when the renal perfusion pressure was allowed to increase. In summary, AT1 activation acutely increases the albumin GSC. This effect appears to be largely independent of changes in the renal perfusion pressure. The AT2 receptor partially attenuates the proteinuric effects of the AT1 receptor.
在这项研究中，我们使用活体显微镜评估了血管紧张素 II 对白蛋白肾小球筛系数 (GSC) 的急性影响。实验在慕尼黑威斯特法伦弗雷默特 (MWF) 大鼠上进行。静脉注射 Alexa-Fluor-594 白蛋白，并测定肾小球毛细血管和鲍曼氏囊内的荧光强度，以计算白蛋白 GSC。在血管紧张素 II（10ng·min(-1)·kg(-1)体重）持续输注之前和期间测量 GSC。基础平均动脉压 (MAP) 为 99 ± 5mmHg，在血管紧张素 II 输注期间稳定在 137 ± 5mmHg。基础 GSC 平均为 0.00044 ± 4.8×10(-5)，血管紧张素 II 输注后增加 286 ± 44%（P<0.0001）。血管紧张素 II 输注期间近端肾小管 Alexa-Fluor-594 白蛋白摄取增加（血管紧张素 II 期间为基础值的 518%，对照期间为 218%；P<0.0001）。在开始血管紧张素 II 输注前注射 AT1 拮抗剂洛沙坦不会引起 GSC 变化。AT2 拮抗剂 PD123319 将基础 GSC 从 0.00052 ± 3.6×10(-5)增加到 0.00074 ± 8.2×10(-5)（P=0.02），而 MAP 没有改变。在有洛沙坦的血管紧张素 II 输注期间，PD123319 将白蛋白 GSC 从 0.00037 ± 5.8×10(-5)增加到 0.00115 ± 0.00015（P=0.001）。当肾脏灌注压被机械控制时，GSC 在血管紧张素 II 输注期间从 0.0007 ± 0.00019 增加到 0.0025 ± 0.00063（P=0.047），与允许肾脏灌注压增加时观察到的情况相似。总之，AT1 激活可急性增加白蛋白 GSC。这种作用似乎在很大程度上与肾脏灌注压的变化无关。AT2 受体部分减弱了 AT1 受体的蛋白尿作用。
