Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice
Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice
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DOI：
10.1152/ajprenal.00019.2008
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发表时间：
2008-09-01
影响因子：
4.2
通讯作者：
Navar, L. G.
中科院分区：
文献类型：
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作者：
Gonzalez-Villalobos, Romer A.;Seth, Dale M.;Navar, L. G.
本研究旨在探讨慢性血管紧张素II(Ang II)对小鼠肾脏血管紧张素II含量和血管紧张素原表达的影响，以及血管紧张素II 1型受体(AT(1)R)在这些变化中的作用。C57BL/6J雄性小鼠给予血管紧张素Ⅱ400或1000 mg·kg(-1)·min(-1)或AT1R阻滞剂(奥美沙坦3 mg·kg(-1)·day(-1))灌胃12天。动脉收缩压和平均动脉压由尾袖体积描记术和放射遥测仪测定。第13天采血和肾脏，用放射免疫分析法检测Ang II，用定量RT-PCR、Western blotting和免疫组织化学方法检测肾组织血管紧张素原的表达。血管紧张素转换酶II在低剂量输注时引起收缩压进行性升高(135+/-2.5毫米汞柱)。相反，高剂量组迅速升高(152+/-2.5，P<；0.05与对照组，109+/-2.8)。Ang II低剂量组(1,203+/-253 fmol/g)和高剂量组(1,258+/-173)与对照组(499+/-40，P<；0.05)相比，肾组织Ang II含量均升高。肾脏血管紧张素原基因和蛋白只有低剂量组分别增加到1.13+/-0.02和1.26+/-0.10，高于对照组(1.00，P<；0.05)。在大剂量输注的小鼠和接受奥美沙坦治疗的小鼠中，没有观察到这些影响。结果表明，慢性Ang II输注增加了小鼠肾内Ang II的含量，两种剂量均出现AT(1)R依赖性摄取，但只有引起缓慢递进反应的低剂量Ang II才会引起AT(1)R依赖性肾内血管紧张素原表达的增加。
The objectives of this study were to determine the effects of chronic angiotensin II (ANG II) infusions on ANG II content and angiotensinogen expression in the mouse kidney and the role of the angiotensin II type 1 receptor (AT(1)R) in mediating these changes. C57BL/6J male mice were subjected to ANG II infusions at doses of 400 or 1,000 ng.kg(-1).min(-1) either alone or with an AT1R blocker (olmesartan; 3 mg.kg(-1).day(-1)) for 12 days. Systolic and mean arterial pressures were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for ANG II determinations by radioimmunoanalysis and intrarenal angiotensinogen expression studies by quantitative RT-PCR, Western blotting, and immunohistochemistry. ANG II infusions at the low dose elicited progressive increases in systolic blood pressure (135 +/- 2.5 mmHg). In contrast, the high dose induced a rapid increase (152 +/- 2.5, P < 0.05 vs. controls, 109 +/- 2.8). Renal ANG II content was increased by ANG II infusions at the low dose (1,203 +/- 253 fmol/g) and the high dose (1,258 +/- 173) vs. controls (499 +/- 40, P < 0.05). Kidney angiotensinogen mRNA and protein were increased only by the low dose to 1.13 +/- 0.02 and 1.26 +/- 0.10, respectively, over controls (1.00, P < 0.05). These effects were not observed in mice infused at the high dose and those receiving olmesartan. The results indicate that chronic ANG II infusions augment mouse intrarenal ANG II content with AT(1)R-dependent uptake occurring at both doses, but only the low dose of infusion, which elicited a slow progressive response, causes an AT(1)R-dependent increase in intrarenal angiotensinogen expression.