Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats
Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats
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DOI：
10.1152/ajprenal.00691.2010
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
--
作者：
Kawarazaki, Hiroo;Ando, Katsuyuki;Fujita, Toshiro
Kawarazaki H，Ando K，Fujita M，Matsui H，Nagae A，Muraoka K，Kawarasaki C，Fujita T.盐皮质激素受体激活：幼鼠盐诱导肾损伤和高血压的主要贡献者。 Am J Physiol Renal Physiol 300：F1402-F1409，2011。首次发表于 2011 年 4 月 6 日； doi:10.1152/ajprenal.00691.2010.-已知过量的盐摄入会优先增加年轻盐敏感高血压人和动物模型的血压 (BP) 并促进肾脏损伤。我们认为盐皮质激素受体（MR）激活在幼年大鼠的肾损伤中发挥着重要作用。比较了喂食高盐 (8.0%) 饮食 4 周的幼年 (3 周龄) 和成年 (10 周龄) 未肾切除 (UNx) Sprague-Dawley 大鼠的血压和尿蛋白。在高盐饮食喂养的年轻 UNx 大鼠中检查了 MR 阻滞剂依普利酮对血压和肾损伤的影响。还测量了肾素-血管紧张素-醛固酮（RAA）系统成分以及炎症和氧化应激标记物的肾脏表达。还研究了血管紧张素受体阻滞剂奥美沙坦（有或没有小剂量醛固酮输注）、醛固酮合酶抑制剂 FAD286 和抗氧化剂 tempol 的作用。与成年大鼠相比，摄入过多的盐会导致幼年大鼠出现更严重的高血压和蛋白尿。年轻高盐大鼠的肾脏表现出明显的组织学损伤、RAA系统成分过度表达以及炎症和氧化应激标志物增加。依普利农治疗显着改善了这些变化。奥美沙坦还可以改善盐引起的肾损伤，但与小剂量醛固酮输注联合使用时效果不佳。 FAD286 和 tempol 也显着降低尿蛋白。年轻时暴露于过量盐的 UNx 大鼠表现出严重的高血压和肾损伤，这可能主要是由于 MR 激活，其次是由于血管紧张素受体激活，这可能是由炎症和氧化应激介导的。
Kawarazaki H, Ando K, Fujita M, Matsui H, Nagae A, Muraoka K, Kawarasaki C, Fujita T. Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats. Am J Physiol Renal Physiol 300: F1402-F1409, 2011. First published April 6, 2011; doi:10.1152/ajprenal.00691.2010.-Excessive salt intake is known to preferentially increase blood pressure (BP) and promote kidney damage in young, salt-sensitive hypertensive human and animal models. We have suggested that mineralocorticoid receptor (MR) activation plays a major role in kidney injury in young rats. BP and urinary protein were compared in young (3-wk-old) and adult (10-wk-old) uninephrectomized (UNx) Sprague-Dawley rats fed a high (8.0%)-salt diet for 4 wk. The effects of the MR blocker eplerenone on BP and renal injury were examined in the high-salt diet-fed young UNx rats. Renal expression of renin-angiotensin-aldosterone (RAA) system components and of inflammatory and oxidative stress markers was also measured. The effects of the angiotensin receptor blocker olmesartan with or without low-dose aldosterone infusion, the aldosterone synthase inhibitor FAD286, and the antioxidant tempol were also studied. Excessive salt intake induced greater hypertension and proteinuria in young rats than in adult rats. The kidneys of young salt-loaded rats showed marked histological injury, overexpression of RAA system components, and an increase in inflammatory and oxidative stress markers. These changes were markedly ameliorated by eplerenone treatment. Olmesartan also ameliorated salt-induced renal injury but failed to do so when combined with low-dose aldosterone infusion. FAD286 and tempol also markedly reduced urinary protein. UNx rats exposed to excessive salt at a young age showed severe hypertension and renal injury, likely primarily due to MR activation and secondarily due to angiotensin receptor activation, which may be mediated by inflammation and oxidative stress.