Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility.
Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility.
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DOI：
10.1371/journal.pone.0193032
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Dimke H
中科院分区：
文献类型：
--
作者：
Laursen SB;Finsen S;Marcussen N;Quaggin SE;Hansen PBL;Dimke H
阻断醛固酮可提供强大的心血管和肾脏保护作用。醛固酮对肾血管内皮细胞(EC)表达的盐皮质激素受体(MR)的影响尚未阐明。我们假设EC中缺乏MR可能对肾脏血管具有保护作用，并通过去除小鼠内皮细胞(EC-MR)中的Nr3c2基因来检验这一点。用留置导管测量清醒小鼠的血压、心率和PAH清除量。在肾动脉和灌流的传入小动脉上，研究了EC中MR对收缩和松弛的作用。用代谢笼测定尿钠排泄量。EC-MR转基因显著降低了分离的主动脉内皮细胞中MR的表达，与Lite(WT)相比。两组间基线和注射血管紧张素转换酶抑制剂后的血压和有效肾血浆流量相似。WT组和EC-MR-KO组的肾动脉收缩和松弛在基础状态下或在血管紧张素转换酶注射2周或4周后无明显差异。传入小动脉的收缩或扩张在不同的基因型间没有差异。应用血管紧张素转换酶抑制剂4周后，两组大鼠的尿钠排泄量、尿白蛋白排泄量和肾脏形态均无明显变化。总之，EC-MR的缺失并不能保护长时间血管输注后的高血压、肾动脉内皮细胞功能障碍或肾功能的发展。
Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused afferent arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC-MR transgenics had markedly decreased MR expression in isolated aortic endothelial cells as compared to littermates (WT). Blood pressure and effective renal plasma flow at baseline and following AngII infusion was similar between groups. No differences in contraction and relaxation were observed between WT and EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of AngII infusion. The constriction or dilatations of afferent arterioles between genotypes were not different. No changes were found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries or renal function following prolonged AngII-infusion.
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影响因子：
8.3
作者：
Lother, Achim;Fuerst, David;Hein, Lutz
通讯作者：
Hein, Lutz
影响因子：
168.9
作者：
Jha, Vivekanand;Garcia-Garcia, Guillermo;Yang, Chih-Wei
通讯作者：
Yang, Chih-Wei
影响因子：
8.3
作者：
Rossi, Gian Paolo;Bernini, Giampaolo;Mantero, Franco
通讯作者：
Mantero, Franco
DOI：
10.1073/pnas.0503878102
发表时间：
2006-01-03
影响因子：
11.1
作者：
Berger, S;Wolfer, DP;Schütz, G
通讯作者：
Schütz, G
影响因子：
8.3
作者：
KATUSIC, ZS;SHEPHERD, JT;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM