Dietary NaCl regulates renal aminopeptidase N: Relevance to hypertension in the Dahl rat

Dietary NaCl regulates renal aminopeptidase N: Relevance to hypertension in the Dahl rat
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DOI:
10.1161/01.hyp.0000111584.15095.8a
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发表时间:
2004-02-01
期刊:
影响因子:
8.3
通讯作者:
Danziger, RS
Danziger, RS
中科院分区:
医学1区
文献类型:
--
作者:
Farjah, M;Washington, TL;Danziger, RS

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氨肽酶N(APN)是肾近端小管细胞刷状缘中丰富的金属水解酶,其将血管紧张素III(Ang III)降解为血管紧张素IV(Ang IV),并且沿着二肽基氨肽酶降解Ang IV。我们研究了高盐饮食对Sprague-Dawley和Dahl盐敏感(SS/Jr)大鼠品系肾脏APN活性和转录丰度的影响。8%盐饮食组和0. 3%盐饮食组的Sprague-Dawley和刘易斯大鼠肾脏APN转录本丰度和蛋白质丰度约为对照组的2倍(P <0. 05; n = 6),提示氨肽酶活性增加可能导致适应高盐饮食时肾脏钠摄取减少。相比之下,Dahl SS/Jr大鼠在8.0%和0.3%盐饮食下肾脏APN转录丰度和活性相同。APN基因的映射,使用辐射杂交面板,1号染色体上的已知的定量位点的Dahl SS/Jr大鼠的血压。结果表明,APN基因是一个很好的候选人盐敏感性在Dahl SS/Jr大鼠。
Aminopeptidase N (APN) is an abundant metallohydrolase in the brush border of kidney proximal tubule cells that degrades angiotensin III (Ang III) to angiotensin IV (Ang IV) and, along with dipeptidylaminopeptidase, degrades Ang IV. We examined the impact of a high-salt diet on renal APN activity and transcript abundance in the Sprague-Dawley and Dahl salt-sensitive (SS/Jr) rat strains. APN transcript abundance and protein abundance were approximate to2-fold greater ( P < 0.05; n = 6) in the kidneys of Sprague-Dawley and Lewis rats ingesting 8% versus 0.3% salt diets, suggesting that increased aminopeptidase activity may contribute to decreased renal sodium uptake during adaptation to a high-salt diet. In contrast, renal APN transcript abundance and activity were the same in Dahl SS/Jr rats ingesting 8.0% versus 0.3% salt diets. The APN gene was mapped, using a radiation-hybrid panel, to known quantitative loci on chromosome 1 for blood pressure in the Dahl SS/Jr rat. The results suggest that the APN gene is a good candidate for salt-sensitivity in the Dahl SS/Jr rat.