Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats.
Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats.
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DOI：
10.1371/journal.pone.0041896
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Nishiyama A
中科院分区：
文献类型：
--
作者：
Kitada K;Nakano D;Liu Y;Fujisawa Y;Hitomi H;Shibayama Y;Shibata H;Nagai Y;Mori H;Masaki T;Kobori H;Nishiyama A
盐皮质激素受体（MR）拮抗剂减轻低血浆醛固酮水平盐敏感性高血压大鼠的肾损伤我们假设氧化应激导致高盐喂养的Dahl盐敏感大鼠MR激活。此外，我们确定了MR激活是否持续并诱导肾损伤，即使在从高盐饮食切换到正常盐饮食之后。高盐喂养4周增加二氢乙锭荧光（DHE，氧化剂生产标记），p22 phox（NADPH氧化酶亚基）和血清和糖皮质激素调节激酶-1（SGK 1，MR转录）在肾小球，与正常盐喂养相比，这些变化持续4周后盐撤出。在高盐饲养期间，Tempol处理（0.5 mmol/L）消除了DHE荧光，p22 phox和SGK 1的变化。高盐饮食4周后减少饮食盐可降低血压和蛋白尿，但在盐减少后4周，蛋白尿明显高于正常对照大鼠。在高盐喂养期间给予tempol，或在盐减少后开始给予MR拮抗剂依普利酮（100 mg/kg/天），在盐减少后4周将蛋白尿恢复至正常水平。百草枯，一种活性氧产生剂，在培养的大鼠肾小球系膜细胞和小鼠足细胞中增强MR转录活性。这些结果表明，氧化应激在Dahl盐敏感大鼠肾小球MR激活中起着重要作用。即使在减少盐摄入量后，持续的MR激活也会限制盐限制的有益效果。
Mineralocorticoid receptor (MR) antagonists attenuate renal injury in salt-sensitive hypertensive rats with low plasma aldosterone levels. We hypothesized that oxidative stress causes MR activation in high-salt-fed Dahl salt-sensitive rats. Furthermore, we determined if MR activation persisted and induced renal injury, even after switching from a high- to a normal-salt diet. High-salt feeding for 4 weeks increased dihydroethidium fluorescence (DHE, an oxidant production marker), p22phox (a NADPH oxidase subunit) and serum and glucocorticoid-regulated kinase-1 (SGK1, an MR transcript) in glomeruli, compared with normal-salt feeding, and these changes persisted 4 weeks after salt withdrawal. Tempol treatment (0.5 mmol/L) during high-salt feeding abolished the changes in DHE fluorescence, p22phox and SGK1. Dietary salt reduction after a 4-week high-salt diet decreased both blood pressure and proteinuria, but was associated with significantly higher proteinuria than in normal control rats at 4 weeks after salt reduction. Administration of tempol during high-salt feeding, or eplerenone, an MR antagonist (100 mg/kg/day), started after salt reduction, recovered proteinuria to normal levels at 4 weeks after salt reduction. Paraquat, a reactive oxygen species generator, enhanced MR transcriptional activity in cultured rat mesangial cells and mouse podocytes. These results suggest that oxidative stress plays an important role in glomerular MR activation in Dahl salt-sensitive rats. Persistent MR activation even after reducing salt intake could limit the beneficial effects of salt restriction.
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影响因子：
8.3
作者：
Funder, John W.
通讯作者：
Funder, John W.
影响因子：
8.3
作者：
Meng, SM;Cason, GW;Manning, RD
通讯作者：
Manning, RD
DOI：
10.1016/s0735-1097(03)00054-8
发表时间：
2003-04-02
影响因子：
24
作者：
Flack, JM;Oparil, S;Saunders, E
通讯作者：
Saunders, E
影响因子：
6.1
作者：
Kawarazaki, Hiroo;Ando, Katsuyuki;Fujita, Toshiro
通讯作者：
Fujita, Toshiro
影响因子：
4.9
作者：
Liu, Gang;Miyata, Kayoko;Nishiyama, Akira
通讯作者：
Nishiyama, Akira