Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats
Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats
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DOI：
10.1681/asn.2004080676
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发表时间：
2005-07-01
影响因子：
13.6
通讯作者：
Nishiyama, A
中科院分区：
文献类型：
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作者：
Kobori, H;Ozawa, Y;Nishiyama, A
本研究旨在确定肾内血管紧张素原增加是否可能导致自发性高血压大鼠 (SHR) 肾血管紧张素 II (Ang II) 的增强和相关组织损伤。 SHR 和 Wistar-Kyoto 大鼠 (WKY) 维持正常饮食，并在 7 周或 14 周龄时处死。两组 SHR 在第 7 周至第 14 周期间接受 Ang II 1 型受体阻滞剂（ARB；奥美沙坦，5 mg/d）或三联疗法（肼屈嗪 7.5 mg/d、利血平 0.15 mg/d 和氢氯噻嗪 3 mg/d [HRHI）。与对照组相比，SHR-14 组 (n = 8) 的收缩压和肾血管紧张素 II 显着升高。 WKY-7、WKY-14 和 SHR-7（各 n = 8）和 ARB 治疗阻止了这些增加（it = 8）。然而，虽然 HRH 治疗可以预防 SHR 中高血压的发生，但这种联合治疗未能降低肾脏 Ang II（it = 8）。使用尿液样本或固定肾切片，通过以下六个参数以半自动方式量化大鼠的肾损伤：（1）尿总蛋白排泄率，（2）肾小球硬化，（3）间质扩张，（4）和（5）间质或肾小球中单核细胞/巨噬细胞的数量，以及（6）动脉增殖。分别通过实时逆转录酶 PCR 和蛋白质印迹分析测量肾皮质中血管紧张素原 mRNA 和蛋白质水平，肾损伤的所有六个参数均同时改变，ARB 治疗也阻止了这些增加。然而，HRH 治疗未能阻止这些增加。这些结果表明，SHR 增强了肾内血管紧张素原的产生，这有助于增加 Ang II 水平，从而导致该菌株发生高血压和肾损伤。
This study was performed to determine whether augmented intrarenal angiotensinogen may contribute to the enhanced renal angiotensin II (Ang II) and associated tissue injury in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were maintained on a normal diet and killed at either 7 or 14 wk of age. Two groups of SHR received either an Ang II type 1 receptor blocker (ARB; olmesartan, 5 mg/d) or a triple therapy (hydralazine 7.5 mg/d, reserpine 0.15 mg/d, and hydrochlorothiazide 3 mg/d [HRHI) during weeks 7 through 14. Systolic BP and renal Ang II were significantly increased in SHR-14 (n = 8) compared with WKY-7, WKY-14, and SHR-7 (n = 8 each), and ARB treatment prevented these increases (it = 8). However, whereas HRH treatment prevented the development of hypertension in SHR, this combination therapy failed to decrease renal Ang II (it = 8). With the use of urine samples or fixed renal sections, renal injuries in rats were quantified in a semiautomated manner by the following six parameters: (1) urinary excretion rate of total protein, (2) glomerular sclerosis, (3) interstitial expansion, (4) and (5) numbers of monocytes/macrophages in interstitium or glomeruli, and (6) arterial proliferation. Angiotensinogen mRNA and protein levels in kidney cortex, measured by real-time reverse transcriptase-PCR and Western blot analysis, respectively, and all six parameters of renal damage were changed in parallel, and ARB treatment also prevented these increases. However, HRH treatment failed to prevent these increases. These results indicate that SHR have enhanced intrarenal angiotensinogen production that contributes to increased Ang II levels leading to the development of hypertension and renal injury in this strain.