Intrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar-Kyoto but not in spontaneously hypertensive rats.
Intrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar-Kyoto but not in spontaneously hypertensive rats.
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DOI：
10.1161/hypertensionaha.108.124198
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Carey RM
中科院分区：
文献类型：
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作者：
Padia SH;Kemp BA;Howell NL;Gildea JJ;Keller SR;Carey RM
在Sprague-Dawley大鼠中，肾AT2Rs介导肾间质（RI） d1样受体（D1R）刺激或RI Ang III输注时的尿钠反应。D1R激活后，顶膜（AM）而非总肾近端小管细胞（RPTC） AT2R表达增加，提示AM AT2R易位可能对尿钠有重要作用。自发性高血压大鼠（SHR）的高血压发病是由肾脏钠排泄缺陷引起的。本研究在Wistar-Kyoto大鼠（WKY）和SHR中检测了at2r介导的RI Ang III输注后的尿钠反应。WKY和SHR在用坎地沙坦（CAND）阻断AT1R 24小时后接受RI Ang III输注。尿钠排泄率（UNaV）由0.043±0.01 μmol/min升高至0.191±0.06 μmol/min (P<0.05)，而在相同条件下，尿钠排泄率没有升高。联合输注PD-123319（一种选择性AT2R拮抗剂）可阻断UNaV的增加。在共聚焦显微镜图像上，与SHR相比，注入Ang iii的WKY显示出更高的RPTC AM AT2R荧光强度（5385±725比919±35，P< 0.0001）， Western blot分析显示WKY中AM（0.050±0.003比0.038±0.003，P<0.01）增加，但没有细胞总AT2R表达。在SHR中，AM AT2R表达对RI Ang III输注的反应保持不变。因此，RI Ang III输注引起WKY的尿钠和RPTC AT2R易位。相同的操作不能诱导SHR中的钠尿或AT2R易位，这表明AT2R介导的钠尿和转运缺陷可能对SHR中高血压的发展很重要。
In Sprague-Dawley rats, renal AT2Rs mediate natriuresis in response to renal interstitial (RI) D1-like receptor (D1R) stimulation or RI Ang III infusion. After D1R activation, apical membrane (AM) but not total renal proximal tubule cell (RPTC) AT2R expression is increased, suggesting that AM AT2R translocation may be important for natriuresis. The onset of hypertension in spontaneously hypertensive rats (SHR) is preceded by defects in renal sodium excretion. The present study examines AT2R-mediated natriuresis in response to RI Ang III infusion in Wistar-Kyoto rats (WKY) and SHR. WKY and SHR received RI Ang III infusion after 24 h of systemic AT1R blockade with candesartan (CAND). In WKY, urine sodium excretion rate (UNaV) increased from 0.043±0.01 to 0.191±0.06 μmol/min (P<0.05) in response to Ang III infusion, but identical conditions failed to increase UNaV in SHR. The increase in UNaV was blocked by co-infusion of PD-123319, a selective AT2R antagonist. On confocal microscopy images, Ang III-infused WKY demonstrated greater RPTC AM AT2R fluorescence intensity compared to SHR (5385±725 vs. 919±35, P<.0001), and Western blot analysis demonstrated increased AM (0.050±0.003 vs. 0.038±0.003, P<0.01) but not total cell AT2R expression in WKY. In SHR, AM AT2R expression remained unchanged in response to RI Ang III infusion. Thus, RI Ang III infusion elicits natriuresis and RPTC AT2R translocation in WKY. Identical manipulations fail to induce natriuresis or AT2R translocation in SHR, suggesting that defects in AT2R-mediated natriuresis and trafficking may be important to the development of hypertension in SHR.