Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys

Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys
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DOI:
10.1161/01.hyp.0000120123.44945.47
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发表时间:
2004-04-01
期刊:
影响因子:
8.3
通讯作者:
Roman, RJ
Roman, RJ
中科院分区:
医学1区
文献类型:
--
作者:
Hoagland, KM;Flasch, AK;Roman, RJ

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本研究比较了Dahl盐敏感大鼠(DS)和耐盐褐挪威大鼠(BN)和经济大鼠(SS.BN13)肾脏中参与钠重吸收调节的酶和转运通道蛋白的表达,其中BN大鼠的13号染色体已渗入到DS遗传背景中。低盐(0.1% NaCl)和高盐(8% NaCl)喂养的DS、BN和SS.BN13大鼠肾皮质中Na+/K+/2Cl(-) (BSC-1)共转运体、Na+/H+交换器(NHE3)和Na+-K+- atp酶蛋白的表达相似。BSC-1和肾外髓K+通道(ROMK)的表达较高,而负责20-羟基二糖四烯酸(20-HETE)形成的细胞色素P4504A蛋白在DS大鼠的肾外髓中的表达低于喂食低盐或高盐饮食的BN或SS.BN13大鼠。此外,与BN和SS.BN13大鼠相比,DS大鼠的肾形成和20-HETE的排泄明显减少。这些结果表明,ROMK和BSC-1在粗升肢中过度表达,并伴有20-HETE的肾形成不足,可能使高盐饮食喂养的Dahl S大鼠易发生Na+潴留和高血压。
This study compared the expression of enzymes and transport and channel proteins involved in the regulation of sodium reabsorption in the kidney of Dahl salt-sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13), in which chromosome 13 from the BN rat has been introgressed into the DS genetic background. The expression of the Na+/K+/2Cl(-) (BSC-1) cotransporter, Na+/H+ exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8% NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a low-salt or a high-salt diet. In addition, the renal formation and excretion of 20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that overexpression of ROMK and BSC-1 in the thick ascending limb combined with a deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high-salt diet to Na+ retention and hypertension.