St Lezin E M, Pravenec M, Wong A L, Liu W, Wang N, Lu S, Jacob H J, Roman R J, Stec D E, Wang J M, Reid I A, Kurtz T W
Department of Laboratory Medicine, University of California, San Francisco 94143, USA.
J Clin Invest. 1996 Jan 15;97(2):522-7. doi: 10.1172/JCI118444.
To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.
为了研究大鼠13号染色体上肾素基因座附近是否存在血压调节基因座，我们将该染色体片段从 Dahl 盐敏感（S）大鼠转移到 Dahl 盐抵抗（R）大鼠的遗传背景上。在携带 S 肾素基因并喂食8%盐饮食的同源 Dahl R 大鼠中，收缩压显著低于祖代 Dahl R 大鼠：分别为127±1 mmHg 和138±4 mmHg（P<0.05）。此外，同源 Dahl R 品系中血压的降低与肾脏肾素 mRNA 的减少和血浆肾素浓度的降低有关。这些发现表明，Dahl S 品系在肾素基因座或其附近携带的等位基因，与 Dahl R 品系中的相应等位基因相比，至少在 Dahl R 大鼠的遗传背景下和高盐饮食环境中研究时，能使血浆肾素浓度和血压更低。自然发生的肾素基因变体在品系间转移后，肾脏肾素 mRNA、血浆肾素浓度和血压同时降低，这强烈表明肾素基因表达的遗传决定变异可影响血压。
