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自发性高血压大鼠的高盐摄入与氨基酸转运体的肾脏表达

High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats.

作者信息

Pinho Maria João, Serrão Maria Paula, Soares-da-Silva Patrício

机构信息

Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal.

出版信息

Am J Physiol Renal Physiol. 2007 May;292(5):F1452-63. doi: 10.1152/ajprenal.00465.2006. Epub 2007 Jan 30.

Abstract

This study evaluated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) the response to salt loading of the renal dopaminergic system and transcript abundance of Na(+)-independent (LAT1 and LAT2) and Na(+)-dependent (ASCT2 and B(0)AT1) amino acid transporters potentially involved in renal tubular uptake of L-DOPA. Rats were fed normal (NS)- or high (HS; 1% saline as drinking water)-salt intake for 24 h. Transcript abundance of amino acid transporters was age dependent, differently regulated in WKY and SHR and responded differently to salt intake. HS intake similarly increased urinary dopamine in 4-wk-old SHR and WKY. At 12 wk of age, HS intake increased urinary dopamine in SHR, but not in WKY. Changes in urinary dopamine paralleled changes in the uptake of l-DOPA in isolated renal tubules from 4- and 12-wk-old WKY and SHR on NS and HS intake. At 12 wk of age, HS intake was accompanied by decreases in LAT1 and LAT2 transcript abundance in WKY and SHR. ASCT2 and B(0)AT1 expression was significantly decreased in both 4- and 12-wk-old WKY and in 4-wk-old SHR on HS intake. By contrast, HS intake increased ASCT2 and B(0)AT1 expression in 12-wk-old SHR. It is concluded that salt-sensitive mechanisms influence LAT1, LAT2, ASCT2, and B(0)AT1 gene transcription. Differences in urinary dopamine and tubular uptake of L-DOPA between WKY and SHR during HS intake, namely in 12-wk-old animals, may result from increases in the ASCT2 and B(0)AT1 mRNA levels and less pronounced decreases in LAT2 expression.

摘要

本研究在自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY)中评估了肾多巴胺能系统对盐负荷的反应,以及可能参与肾小管摄取左旋多巴的钠非依赖性(LAT1和LAT2)和钠依赖性(ASCT2和B(0)AT1)氨基酸转运体的转录丰度。大鼠分别给予正常盐(NS)或高盐(HS;1%盐水作为饮用水)摄入24小时。氨基酸转运体的转录丰度具有年龄依赖性,在WKY和SHR中受到不同调节,并且对盐摄入的反应也不同。高盐摄入使4周龄的SHR和WKY的尿多巴胺同样增加。在12周龄时,高盐摄入使SHR的尿多巴胺增加,但WKY未增加。4周龄和12周龄的WKY和SHR在正常盐和高盐摄入情况下,尿多巴胺的变化与离体肾小管中左旋多巴摄取的变化平行。在12周龄时,高盐摄入使WKY和SHR的LAT1和LAT2转录丰度降低。高盐摄入使4周龄和12周龄的WKY以及4周龄的SHR的ASCT2和B(0)AT1表达显著降低。相比之下,高盐摄入使12周龄的SHR的ASCT2和B(0)AT1表达增加。结论是盐敏感机制影响LAT1、LAT2、ASCT2和B(0)AT1基因转录。在高盐摄入期间,即12周龄动物中,WKY和SHR之间尿多巴胺和肾小管左旋多巴摄取的差异可能是由于ASCT2和B(0)AT1 mRNA水平升高以及LAT2表达下降不太明显所致。

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