Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats
Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats
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DOI：
10.1093/ndt/gfq197
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发表时间：
2010-09-01
影响因子：
6.1
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
--
作者：
Kawarazaki, Hiroo;Ando, Katsuyuki;Fujita, Toshiro
背景青春期前摄入过多的盐会永久性地增加血压（BP）。我们研究了盐皮质激素受体（MR）在青春期前Dahl盐敏感（SS）大鼠盐诱导的高血压和肾损害中的作用。对青春期前（6周龄）和成年（10周龄）Dahl SS大鼠喂食高盐（8.0%）饮食10周后的血压和肾功能进行了比较。在4至10周龄之间使用MR拮抗剂依普利酮的治疗效果（食物中0.125%），血管扩张剂肼苯哒嗪（饮用水中50 mg/kg/天）或超氧化物歧化酶模拟物4-羟基-2，2，6，6-四甲基-哌啶-N-氧基（tempol）结果：（1）高脂饲料喂养青春期前大鼠10周后，高脂饲料（0.6 mmol/kg/d，饮水）对大鼠血压和肾功能的影响。与成年期相比，青春期前开始的过量盐摄入与更高的血压升高和更大的蛋白尿相关。依普利酮在青春期前大鼠给药期间适度降低血压并显著改善肾损伤。这些影响在停药后持续存在。肼苯哒嗪可显著降低血压和减少蛋白尿，但停药后这些作用完全消失。过量盐增加尿8-羟基-2 '-脱氧鸟苷水平、肾内巨噬细胞浸润和肾纤溶酶原激活物抑制剂-1和转化生长因子-β mRNA表达。依普利酮，而不是肼屈嗪，减弱这些盐诱导的炎症反应。Tempol可改善盐性高血压和肾损伤，即使在停药后也是如此。Dahl SS大鼠暴露于过量的盐在青春期前表现出永久性增加的易感性盐诱导的高血压和蛋白尿。MR激活可能至少部分通过诱导氧化和炎症来促进这些效应。
Background. Excessive prepubertal salt intake permanently increases blood pressure (BP). We examined the role that the mineralocorticoid receptor (MR) plays in the salt-induced hypertension and renal damage of prepubertal Dahl salt-sensitive (SS) rats.Methods. Prepubertal (6 weeks old) and adult (10 weeks old) Dahl SS rats fed a high (8.0%) salt (HS) diet for 10 weeks were compared in terms of BP and renal function. The effect of treatment between the ages of 4 and 10 weeks with the MR antagonist eplerenone (0.125% in chow), the vasodilator hydralazine (50 mg/kg/day in drinking water) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (tempol) (0.6 mmol/kg/day in drinking water) on the BP and renal function of prepubertal rats fed a HS diet for 10 weeks was also examined.Results. Excessive salt intake starting in prepuberty was associated with a higher BP increase and greater proteinuria than if it started in adulthood. Eplerenone moderately reduced BP and markedly improved renal injury during its administration in prepubertal rats. These effects continued after drug discontinuation. Hydralazine greatly decreased BP and reduced proteinuria, but these effects were completely lost after drug discontinuation. Excessive salt increased urinary 8-hydroxy-2'-deoxyguanosine levels, intrarenal macrophage infiltration and renal plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA expression. Eplerenone, but not hydralazine, attenuated these salt-induced inflammatory reactions. Tempol improved salt-induced hypertension and renal injury, even after its discontinuation.Conclusions. Dahl SS rats exposed to excessive salt in prepubescence show a permanent increase in susceptibility to salt-induced hypertension and proteinuria. MR activation may promote these effects at least in part by inducing oxidation and inflammation.