Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production
Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production
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DOI：
10.1046/j.1523-1755.2002.00155.x
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发表时间：
2002-02-01
影响因子：
19.6
通讯作者：
Navar, LG
中科院分区：
文献类型：
--
作者：
Kobori, H;Harrison-Bernard, LM;Navar, LG
背景资料。在维持高盐饮食(His)以抑制基础肾血管紧张素原水平的大鼠中，血管紧张素II(Ang II)输注13天可增加肾脏血管紧张素原的mRNA和蛋白，从而为进一步提高肾内Ang II水平提供了机制。本研究验证了这样一种假说，即在血管紧张素Ⅱ输注过程中，肾内血管紧张素原的形成增加是通过分泌到肾小管液中，导致尿中血管紧张素原排泄增加。观察慢性血管紧张素Ⅱ(Ang II)灌胃对雄性SD大鼠(n=10)肾脏和血浆Ang II水平及uAGT的影响。其中一组(H/S+Ang 11，N=5)给予Ang II 40 ng/min，另一组(H/S+Sham，N=5)为假手术组。另设正常盐饮食对照组和假手术组(N/S+Sham，N=5)。H/S单独给药对大鼠的收缩压无明显影响(103+/-2vs.104+/-2 mm Hg)，而血管紧张素Ⅱ对H/S大鼠的收缩压在2周后显著升高，从103+/-2升至154+/-2。H/S+Ang II组肾组织Ang II含量显著高于H/S+Sham组(435+/-153vs.65+/-14fmol/g)。与Sham相比，Ang II输注显著增加uAGT(放射免疫法测定生成Ang I的浓度为4.0+/-0.5vs.1.0+/-0.2nmolAng I/day；Western blotting分析测定uAGT为57+/-15vs.14+/-2个单位)。放射免疫法测定的U-AGT与肾脏血管紧张素Ⅱ含量高度相关(r=0.79)，与血浆血管紧张素Ⅱ浓度无相关性(r=0.20)。这些数据表明，慢性Ang II输注增加了尿中血管紧张素原的排泄率，并提示uAGT为Ang II依赖型高血压肾内血管紧张素原的产生提供了一个特异的指标。
Background. In rats maintained on a high salt diet (HIS) to suppress basal renal angiotensinogen levels, angiotensin II (Ang II) infusion for 13 days increased renal angiotensinogen mRNA and protein, thus providing a mechanism for further augmentation of intrarenal Ang II levels. The present study tested the hypothesis that enhanced intrarenal angiotensinogen formation during Ang II infusion is reflected by secretion into the tubular fluid leading to increased urinary excretion of angiotensinogen (U-AGT).Methods. The effects of chronic Ang II infusion were examined on kidney and plasma Ang II levels and UAGT in male Sprague-Dawley rats maintained on an 8% salt diet for three weeks (N = 10). Following one week on the H/S diet, Ang II (40 ng/min) was administered for two weeks via an osmotic minipump to one group (H/S + Ang 11, N = 5), while the remaining rats were sham-operated (H/S + Sham, N = 5). Additionally, a control group was prepared with normal salt diet and sham-operation (N/S + Sham, N = 5).Results. H/S alone did not alter systolic blood pressure (BP) (103 +/- 2 vs. 104 +/- 2 mm Hg), while Ang II infusion to H/S rats significantly increased systolic BP from 103 +/- 2 to 154 +/- 2 after two weeks. Intrarenal Ang II content in H/S + Ang II was significantly greater than H/S + Sham (435 +/- 153 vs. 65 +/- 14 fmol/g). Ang II infusion significantly increased UAGT (4.0 +/- 0.5 vs. 1.0 +/- 0.2 nmol Ang I/day by radioimmunoassay of generated Ang I; 57 +/- 15 vs. 14 +/- 2 densitometric units by Western blotting analysis) compared to Sham. U-AGT by radioimmunoassay was highly correlated with kidney Ang II content (r = 0.79); but not with plasma Ang II concentration (r = 0.20).Conclusions. These data demonstrate that chronic Ang II infusion increases urinary excretion rate of angiotensinogen, and suggest that UAGT provides a specific index of intrarenal angiotensinogen production in Ang II-dependent hypertension.