Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.
Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.
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DOI：
10.1371/journal.pone.0026994
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chung SK
中科院分区：
文献类型：
--
作者：
Leung JW;Wong WT;Koon HW;Mo FM;Tam S;Huang Y;Vanhoutte PM;Chung SS;Chung SK
内皮素-1（ET-1）是一种强有力的血管收缩剂，参与血管张力的调节，并与高血压有关。然而，小血管内皮细胞ET-1在高血压中的作用尚不清楚。本研究采用转基因小鼠方法，观察内皮细胞ET-1慢性过度表达对动脉血压和血管反应性的影响。转基因小鼠（泰特-1）内皮细胞ET-1过表达，肺小血管内皮细胞ET-1水平升高。尽管泰特-1小鼠表现正常，但它们发展为轻度高血压，其通过ETA受体（BQ 123）而不是ETB受体（BQ 788）拮抗剂正常化。尾袖测量显示清醒泰特-1小鼠的收缩压和平均血压显著升高。小鼠还表现出左心室肥大和心电图左轴偏移，表明外周阻力增加。在8周龄的泰特-1小鼠中，尿和血清中的离子浓度是正常的，这表明系统性高血压与肾功能无关，尽管较高的血清尿素水平提示肾功能障碍的发生。在泰特-1小鼠中，主动脉和肠系膜动脉的血管反应性改变，表明慢性内皮ET-1上调导致导管和阻力动脉中的血管张力失衡。这些结果为ET-1在内皮细胞中的空间表达在轻度高血压中的作用是通过ETA受体介导的提供了证据。结果还表明，慢性内皮ET-1过度表达影响心脏和血管功能，这至少部分导致血压升高。
Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ETA receptor (BQ123) but not by ETB receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ETA receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation.
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影响因子：
8.3
作者：
LARIVIERE, R;DAY, R;SCHIFFRIN, EL
通讯作者：
SCHIFFRIN, EL
影响因子：
4.9
作者：
Amiri, Farhad;Paradis, Pierre;Schiffrin, Ernesto L.
通讯作者：
Schiffrin, Ernesto L.
DOI：
10.1006/bbrc.1995.2560
发表时间：
1995-10-24
影响因子：
3.1
作者：
MANSOOR, AM;HONDA, M;MITSUI, Y
通讯作者：
MITSUI, Y
影响因子：
13.6
作者：
Quaschning, Thomas;Voss, Florian;Hocher, Berthold
通讯作者：
Hocher, Berthold
影响因子：
37.8
作者：
Amiri, F;Virdis, A;Schiffrin, EL
通讯作者：
Schiffrin, EL