Wang Q, Hummler E, Maillard M, Nussberger J, Rossier B C, Brunner H R, Burnier M
Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland.
Kidney Int. 2001 Jun;59(6):2216-21. doi: 10.1046/j.1523-1755.2001.00739.x.
In mice, a partial loss of function of the epithelial sodium channel (ENaC), which regulates sodium excretion in the distal nephron, causes pseudohypoaldosteronism, a salt-wasting syndrome. The purpose of the present experiments was to examine how alpha ENaC knockout heterozygous (+/-) mice, which have only one allele of the gene encoding for the alpha subunit of ENaC, control their blood pressure (BP) and sodium balance.
BP, urinary electrolyte excretion, plasma renin activity, and urinary adosterone were measured in wild-type (+/+) and heterozygous (+/-) mice on a low, regular, or high sodium diet. In addition, the BP response to angiotensin II (Ang II) and to Ang II receptor blockade, and the number and affinity of Ang II subtype 1 (AT1) receptors in renal tissue were analyzed in both mouse strains on the three diets.
In comparison with wild-type mice (+/+), alpha ENaC heterozygous mutant mice (+/-) showed an intact capacity to maintain BP and sodium balance when studied on different sodium diets. However, no change in plasma renin activity was found in response to changes in sodium intake in alpha ENaC +/- mice. On a normal salt diet, heterozygous mice had an increased vascular responsiveness to exogenous Ang II (P < 0.01). Moreover, on a normal and low sodium intake, these mice exhibited an increase in the number of AT1 receptors in renal tissues; their BP lowered markedly during the Ang II receptor blockade (P < 0.01) and there was a clear tendency for an increase in urinary aldosterone excretion.
alpha ENaC heterozygous mice have developed an unusual mechanism of compensation leading to an activation of the renin-angiotensin system, that is, the up-regulation of AT1 receptors. This up-regulation may be due to an increase in aldosterone production.
在小鼠中，调节远端肾单位钠排泄的上皮钠通道（ENaC）功能部分丧失会导致假性醛固酮减少症，这是一种失盐综合征。本实验的目的是研究仅具有编码ENaCα亚基基因的一个等位基因的αENaC基因敲除杂合子（+/-）小鼠如何控制其血压（BP）和钠平衡。
在低钠、正常或高钠饮食的野生型（+/+）和杂合子（+/-）小鼠中测量血压、尿电解质排泄、血浆肾素活性和尿醛固酮。此外，在三种饮食条件下，对两种小鼠品系分析了对血管紧张素II（Ang II）和Ang II受体阻断的血压反应，以及肾组织中Ang II 1型（AT1）受体的数量和亲和力。
与野生型小鼠（+/+）相比，αENaC杂合突变小鼠（+/-）在不同钠饮食条件下研究时显示出维持血压和钠平衡的完整能力。然而，在αENaC +/-小鼠中，未发现血浆肾素活性随钠摄入量变化而改变。在正常盐饮食下，杂合子小鼠对外源性Ang II的血管反应性增加（P < 0.01）。此外，在正常和低钠摄入时，这些小鼠肾组织中AT1受体数量增加；在Ang II受体阻断期间其血压显著降低（P < 0.01），并且尿醛固酮排泄有明显增加趋势。
αENaC杂合小鼠已形成一种不寻常的代偿机制，导致肾素-血管紧张素系统激活，即AT1受体上调。这种上调可能是由于醛固酮产生增加所致。
