Angiotensin AT₂ receptor stimulation inhibits early renal inflammation in renovascular hypertension.
Angiotensin AT₂ receptor stimulation inhibits early renal inflammation in renovascular hypertension.
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DOI：
10.1161/hypertensionaha.110.164202
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Siragy HM
中科院分区：
文献类型：
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作者：
Matavelli LC;Huang J;Siragy HM
血管紧张素II 2型受体（AT 2 R）抵消血管紧张素II 1型受体（AT 1 R）的大多数作用。我们假设直接刺激AT 2 R可减少2肾1夹（2K 1C）高血压大鼠模型肾脏炎症细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和转化生长因子-β1（TGF-β1）的产生，并增加一氧化氮（NO）和环鸟苷酸（cGMP）的产生。我们使用Sprague-Dawley大鼠评价了用溶剂、AT 2 R激动剂化合物21（C21）或AT 2 R拮抗剂PD 123319（PD）单独和联合给药4天的假手术和2K 1C大鼠中TNF-α、IL-6、NO和cGMP的肾间质液恢复水平的变化; AT 1 R、AT 2 R、TGF-β1、TNF-α和IL-6的肾表达（每组n=6）。在2K 1C中，收缩压显著升高，并且不受任何治疗的影响。夹闭组肾组织中AT 1 R、AT 2 R、TNF-α、IL-6、TGF-β1的表达显著增加，NO和cGMP水平显著降低。这些因素不受PD治疗的影响。C21组肾组织TNF-α、IL-6、TGF-β1水平明显降低，NO和cGMP水平明显升高。C21和PD联合治疗部分逆转了观察到的C21效应。与假手术组相比，2K 1C动物未夹肾中TNF-α、IL-6、TGF-β1、NO或cGMP无显著变化。我们的结论是，直接AT 2 R刺激减少早期肾脏炎症反应，提高生产的NO和cGMP在肾血管性高血压独立的血压降低。
Angiotensin II type 2 receptor (AT2R) counteracts most effects of angiotensin II type 1 receptor (AT1R). We hypothesized that direct AT2R stimulation reduces renal production of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β1 (TGF-β1) and enhances the production of nitric oxide (NO) and cyclic guanosine 3′,5′-monophosphate (cGMP) in the clipped kidney of 2-kidney, 1-clip (2K1C) hypertension rat model. We used Sprague-Dawley rats to evaluate changes in renal interstitial fluid recovery levels of TNF-α, IL-6, NO, and cGMP; renal expression of AT1R, AT2R, TGF-β1, TNF-α, and IL-6 in sham and 2K1C rats treated for 4 days with vehicle, AT2R agonist compound 21 (C21), or AT2R antagonist PD123319 (PD), alone and combined (n=6, each group). Systolic blood pressure increased significantly in 2K1C and was not influenced by any treatment. Clipped kidneys showed significant increases in renal expression of AT1R, AT2R, TNF-α, IL-6, TGF-β1 and decreases in NO and cGMP levels. These factors were not influenced by PD treatment. In contrast, C21 caused significant decrease in renal TNF-α, IL-6, TGF-β1 and an increase in NO and cGMP levels. Combined C21 and PD treatment partially reversed the observed C21 effects. Compared to sham, there were no significant changes in TNF-α, IL-6, TGF-β1, NO, or cGMP in the nonclipped kidneys of 2K1C animals. We conclude that direct AT2R stimulation reduces early renal inflammatory responses and improves production of NO and cGMP in renovascular hypertension independent of blood pressure reduction.