Differential regulation of angiotensin II receptor subtypes in rat kidney by low dietary sodium.

Differential regulation of angiotensin II receptor subtypes in rat kidney by low dietary sodium.
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低钠饮食对大鼠肾脏血管紧张素 II 受体亚型的差异调节。

DOI:
10.1161/01.hyp.25.4.872
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发表时间:
1995
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
Wang,DH
Wang,DH
中科院分区:
--
文献类型:
--
作者:
Du,Y;Yao,A;Guo,D;Inagami,T;Wang,DH

文献摘要

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本研究旨在确定编码两种已知的血管紧张素 II 1 型 (AT1) 受体亚型(AT1A 和 AT1B)的肾脏信使 RNA (mRNA) 的表达是否可以通过膳食钠进行调节。七周大的雄性 Wistar 大鼠被喂食低钠饮食(0.07%,n=9)或正常钠饮食(0.5%,n=9 [对照])14 天。大鼠 AT1 互补 DNA (cDNA) 探针可与编码 AT1A 和 AT1B 受体亚型的 mRNA 杂交,而 cDNA 探针则对 AT1A 或 AT1B mRNA 具有选择性,用于 Northern 印迹或原位杂交分析。通过使用 Northern 印迹分析,发现喂食低钠饮食的大鼠中 AT1 和 AT1A 受体的肾脏 mRNA 水平与对照相比增加了一倍 (P<.05)。由于Northern印迹分析未检测到肾AT1BmRNA含量,因此使用由AT1BcDNA制成的地高辛标记的cRNA探针进行原位杂交的定量图像分析。原位杂交分析表明,在正常钠饮食的大鼠中,AT1BmRNA 在肾近端肾小管和集合管中表达。与对照饮食相比,低钠饮食显着降低了肾皮质(5.51±0.77% vs 2.73±0.35%,P<.05)和髓质(4.76±0.70% vs 2.01±0.43%,P<.05)AT1BmRNA阳性染色面积百分比。这些结果表明,低钠摄入引起的肾脏中 AT1mRNA 水平的增加是 AT1AmRNA 选择性增加的结果,并表明 AT1A 是肾脏中 AT1 的主要受体亚型。数据还表明,饮食中的钠会差异性地调节编码 AT1 受体亚型的基因的表达,因为 AT1A 和 AT1B 亚型的表达对低钠饮食的反应呈负相关。讨论了功能含义。
This study was designed to determine whether expression of renal messenger RNA (mRNA) encoding the two known angiotensin II type 1 (AT1) receptor subtypes (AT1Aand AT1B) can be regulated by dietary sodium. Seven-week-old male Wistar rats were fed a low-sodium diet (0.07%, n=9) or a normal-sodium diet (0.5%, n=9 [control]) for 14 days. A rat AT1complementary DNA (cDNA) probe, which hybridizes to mRNA encoding both the AT1Aand AT1Breceptor subtypes, and cDNA probes, which are selective for AT1Aor AT1BmRNA, were used in Northern blot or in situ hybridization analysis. By use of Northern blot analysis, renal mRNA levels for the AT1and AT1Areceptors in rats fed a low-sodium diet were found to be increased twofold (P<.05) compared with control. Because renal AT1BmRNA content was not detected by Northern blot analysis, quantitative image analysis of in situ hybridization with a digoxigenin-labeled cRNA probe made from AT1BcDNA was used. In situ hybridization analysis indicated that AT1BmRNA was expressed in the proximal and collecting tubules of the kidney in rats fed a normal-sodium diet. The low-sodium diet significantly decreased the percent positive staining area of AT1BmRNA in the renal cortex (5.51±0.77% versus 2.73±0.35%,P<.05) and medulla (4.76±0.70% versus 2.01±0.43%,P<.05) compared with the control diet. These results indicate that the increase in AT1mRNA levels in the kidney induced by low sodium intake is the result of a selective increase in AT1AmRNA and suggest that AT1Ais the predominant receptor subtype of AT1in the kidney. The data also suggest that dietary sodium differentially modulates the expression of genes encoding AT1receptor subtypes, because there is an inverse relationship between the expression of the AT1Aand AT1Bsubtypes in response to a low-sodium diet. The functional implications are discussed.