ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.
ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.
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DOI：
10.1111/apha.12397
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Pollock DM
中科院分区：
文献类型：
--
作者：
Heimlich JB;Speed JS;Bloom CJ;O'Connor PM;Pollock JS;Pollock DM
目前的研究旨在确定来自内皮细胞的ET-1是否有助于高盐饮食和/或缺氧小鼠肾小球的氧化应激。C57BL6/J对照小鼠或血管内皮细胞ET-1敲除（VEET KO）小鼠在代谢笼评估肾功能和分离肾小球以测定活性氧（ROS）之前，先暴露于缺氧（8% O2） 3小时和高盐饮食（4% NaCl） 2周。在对照组小鼠中，缺氧在最初的24小时内显著增加尿蛋白的排泄，但仅限于高盐饮食的小鼠。在对照组中，缺氧增加了肾小球ET-1 mRNA的表达，而在血管内皮细胞ET-1敲除（VEET KO）小鼠中则没有。在正常条件下，高盐饮食小鼠肾小球ET-1 mRNA的表达比正常盐饮食小鼠高约150% （p<0.05）。高盐饮食管理显著增加了流量控制的肾小球ROS的产生，但在VEET KO小鼠分离的肾小球中没有。在C57BL6/J小鼠中，ETA受体选择性拮抗剂ABT-627显著降低高盐饮食引起的肾小球ROS生成的增加。此外，长期给C57BL6/J小鼠注入亚压剂量的ET-1（渗透泵）显著增加了被ETA拮抗剂治疗阻止的肾小球ROS水平。这些数据表明，缺氧和高盐饮食通过内皮来源的ET-1- eta受体激活增加肾小球ROS的产生，并提供ET-1诱导肾病的潜在机制。
The current study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high salt diet and/or hypoxia. C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to three-hour exposure to hypoxia (8% O2) and or 2 weeks of high salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for determination of reactive oxygen species (ROS). In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 hrs, but only in animals on a high salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high salt diet had approximately 150% higher glomerular ET-1 mRNA expression compared to a normal salt diet (p<0.05). High salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor selective antagonist, ABT-627, significantly attenuated the increase in glomerular ROS production produced by high salt diet. In addition, chronic infusion of C57BL6/J mice with a sub-pressor dose of ET-1 (osmotic pumps) significantly increased levels of glomerular ROS that were prevented by ETA antagonist treatment. These data suggest that both hypoxia and a high salt diet increases glomerular ROS production via endothelial derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1 induced nephropathy.
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DOI：
10.1161/hypertensionaha.110.156570
发表时间：
2010-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
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作者：
Saleh MA;Boesen EI;Pollock JS;Savin VJ;Pollock DM
通讯作者：
Pollock DM
影响因子：
15.9
作者：
Ahn, D;Ge, YQ;Kohan, DE
通讯作者：
Kohan, DE
影响因子：
8.3
作者：
Elmarakby, AA;Loomis, ED;Pollock, DM
通讯作者：
Pollock, DM
DOI：
10.1097/01.asn.0000092145.90389.65
发表时间：
2003-11-01
影响因子：
13.6
作者：
Kitiyakara, C;Chabrashvili, T;Wilcox, CS
通讯作者：
Wilcox, CS
影响因子：
19.6
作者：
通讯作者：
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