Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention
Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention
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DOI：
10.1152/ajprenal.00190.2006
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发表时间：
2006-12-01
影响因子：
4.2
通讯作者：
Kohan, Donald E.
中科院分区：
文献类型：
--
作者：
Ge, Yuqiang;Bagnall, Alan;Kohan, Donald E.
集合管（CD）衍生的内皮素-1（ET-1）抑制肾脏钠重吸收，其缺乏会升高血压（BP）。CD内皮素B（ET B）受体在介导这些效应中的作用尚不清楚。使用水通道蛋白-2启动子-Cre重组酶转基因和loxP侧翼ETB受体基因（CD ETB KO）实现ETB受体的CD特异性敲除。在正常和高盐饮食期间，比较了CD特异性敲除ETB受体、ETA受体（CD ETA KO）和ET-1（CD ET-1 KO）的小鼠及其各自对照组的Sylobin BP。在正常的钠饮食中，CD ETB KO小鼠的血压升高，在高盐饮食期间血压进一步升高。然而，CD ETB KO小鼠的高血压程度和盐喂养期间血压的进一步升高低于CD ET-1 KO小鼠，而CD ETA KO小鼠血压正常。CD ETB KO小鼠在急性钠负荷后钠排泄受损。在正常和高钠饮食的CD ETB KO小鼠中，醛固酮和血浆肾素活性降低，而血浆和尿ET-1水平与对照组无差异。总之，CD ETB受体部分介导ET-1的降压和利钠作用。CD ETA和ETB受体不能完全解释CD衍生的ET-1的抗高血压和利钠利尿作用，表明该肽的旁分泌作用。
Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and its deficiency increases blood pressure (BP). The role of CD endothelin B (ETB) receptors in mediating these effects is unknown. CD-specific knockout of the ETB receptor was achieved using an aquaporin-2 promoter-Cre recombinase transgene and the loxP-flanked ETB receptor gene (CD ETB KO). Systolic BP in mice with CD-specific knockout of the ETB receptor, ETA receptor (CD ETA KO) and ET-1 (CD ET-1 KO), and their respective controls were compared during normal- and high-salt diet. On a normal- sodium diet, CD ETB KO mice had elevated BP, which increased further during high salt feeding. However, the degree of hypertension in CD ETB KO mice and the further increase in BP during salt feeding were lower than that of CD ET-1 KO mice, whereas CD ETA KO mice were normotensive. CD ETB KO mice had impaired sodium excretion following acute sodium loading. Aldosterone and plasma renin activity were decreased in CD ETB KO mice on normal- and high-sodium diets, while plasma and urinary ET-1 levels did not differ from controls. In conclusion, the CD ETB receptor partially mediates the antihypertensive and natriuretic effects of ET-1. CD ETA and ETB receptors do not fully account for the antihypertensive and natriuretic effects of CD-derived ET-1, suggesting paracrine effects of this peptide.