Receptor-mediated intrarenal angiotensin II augmentation in angiotensin II-infused rats.
Receptor-mediated intrarenal angiotensin II augmentation in angiotensin II-infused rats.
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DOI：
10.1161/01.hyp.28.4.669
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发表时间：
1996-10
期刊：
影响因子：
8.3
通讯作者：
L. Zou;J. Imig;A. V. Thun;A. Hymel;H. Ono;L. Navar
中科院分区：
文献类型：
--
作者：
L. Zou;J. Imig;A. V. Thun;A. Hymel;H. Ono;L. Navar
慢性低剂量血管紧张素II（Ang II）输注13天模拟两肾一夹Goldblatt高血压并增加肾内Ang II水平。我们进行了研究，以确定增强肾内血管紧张素II水平的时间进程，以及增加肾内血管紧张素II是否是一个组织特异性事件，需要一个受体介导的步骤。将雄性Sprague-Dawley大鼠单侧肾切除，并通过皮下渗透微型泵输注载体或Ang II（40 ng/min）。在微型泵植入后3、7、10和13天测量血浆和肾脏Ang II水平。与对照组（126 +/- 2 mm Hg）相比，血管紧张素II输注大鼠的收缩压在第6天显示出可检测的增加（146 +/- 2 mm Hg），并在第12天继续增加至189 +/- 5 mm Hg。血浆血管紧张素II水平升高的第3天，而肾内血管紧张素II水平没有显着升高，直到10天的血管紧张素II输注。肾损伤的特点是局灶性和节段性肾小球硬化是明显的血管紧张素II输注后13天。氯沙坦（30 mg/kg/天）在输注期间（125 +/- 1 mm Hg）预防Ang II输注大鼠高血压的发展，并降低肾小球损伤的程度。血浆肾素活性在血管紧张素II输注组受到抑制，但在两个氯沙坦治疗组显着升高。血浆血管紧张素II水平升高，血管紧张素II输注大鼠，甚至更高，在氯沙坦治疗。在输注Ang II的大鼠中，肾内Ang II水平显著增加（354 +/- 60 vs. 164 +/- 23 fmol/g）。然而，氯沙坦治疗阻止了由Ang II输注引起的肾内Ang II的增加。心脏和肾上腺血管紧张素II水平没有显着增加血管紧张素II输注大鼠，但显着升高氯沙坦治疗期间。这些结果表明，慢性血管紧张素II输注引起的肾内血管紧张素II水平的组织特异性升高是由血管紧张素1型受体激活介导的，这导致受体介导的血管紧张素II内化，增强肾内血管紧张素II形成，或两者兼而有之。
Chronic low-dose angiotensin II (Ang II) infusion for 13 days mimics two-kidney, one clip Goldblatt hypertension and increase intrarenal Ang II levels. We performed studies to determine the time course for the enhancement of intrarenal Ang II levels and whether the increased intrarenal Ang II is a tissue-specific event and requires a receptor-mediated step. Male Sprague-Dawley rats were uninephrectomized, and either vehicle or Ang II (40 ng/min) was infused via a subcutaneous osmotic minipump. Plasma and renal Ang II levels were measured 3, 7, 10, and 13 days after minipump implantation. Compared with controls (126 +/- 2 mm Hg), systolic pressure in Ang II-infused rats exhibited a detectable increase by day 6 (146 +/- 2 mm Hg) and continued to increase to 189 +/- 5 mm Hg by day 12. Plasma Ang II levels were elevated by day 3, whereas intrarenal Ang II levels were not significantly elevated until 10 days of Ang II infusion. Renal injury characterized by focal and segmental glomerulosclerosis was evident after 13 days of Ang II infusion. Losartan (30 mg/kg per day) prevented the development of hypertension in the Ang II-infused rats for the duration of the infusion period (125 +/- 1 mm Hg) and reduced the degree of glomerular injury. Plasma renin activity was suppressed in the Ang II-infused group but was elevated markedly in both losartan-treated groups. Plasma Ang II levels were elevated in the Ang II-infused rats and were even higher during losartan treatment. Intrarenal Ang II levels were enhanced significantly (354 +/- 60 versus 164 +/- 23 fmol/g) in the Ang II-infused rats. However, losartan treatment prevented the augmentation of intrarenal Ang II caused by Ang II infusion. Heart and adrenal Ang II levels were not significantly increased in the Ang II-infused rats but were significantly elevated during losartan treatment. These results suggest that the tissue-specific elevations of intrarenal Ang II levels caused by chronic Ang II infusion are mediated by angiotensin type 1 receptor activation, which leads to either receptor-mediated internalization of Ang II, enhancement of intrarenal Ang II formation, or both.