Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice.
Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice.
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DOI：
10.1006/bbrc.1999.0500
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发表时间：
1999-04
影响因子：
3.1
通讯作者：
Masami Tanaka;Shinya Tsuchida;T. Imai;N. Fujii;Hitoshi Miyazaki;Toshihiro Ichiki;Mitsuhide Naruse;Tadashi Inagami
中科院分区：
文献类型：
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作者：
Masami Tanaka;Shinya Tsuchida;T. Imai;N. Fujii;Hitoshi Miyazaki;Toshihiro Ichiki;Mitsuhide Naruse;Tadashi Inagami
AT2基因缺失的小鼠血压升高，对血管紧张素II(Ang II)的升压反应被夸大。本研究的目的是阐明小鼠对血管紧张素转换酶II反应增强的机制。AT2基因缺失小鼠血管紧张素转换酶II引起的主动脉条收缩明显大于对照组，AT1拮抗剂氯沙坦可完全阻断血管紧张素转换酶的作用。AT2基因缺失组小鼠主动脉AT1受体含量(212+/-58.2fmol/mg蛋白)显著高于对照组(98.2+/-55.9fmol/mg蛋白)(P<；0.05，n=5)。AT1和AT2mRNAs在对照组小鼠的主动脉中均有表达，而在AT2基因敲除小鼠中仅有AT1mRNA的表达。AT2基因敲除小鼠的AT1mRNA表达显著高于对照组(1.5倍，P<；0.05，n=5)。本研究清楚地表明，AT2基因敲除小鼠血管对Ang II的反应性增加至少部分是由于血管AT1受体表达增加，并提示AT2通过AT1受体之间的串扰下调AT1受体而抵消Ang II的血管作用，机制尚不清楚。
Blood pressure is elevated and pressor response to angiotensin II (Ang II) is exaggerated in AT2 null mice. The purpose of the present study was to elucidate the mechanism for the increased responsiveness to Ang II in the mice. The contraction of aortic strips generated by Ang II was significantly greater in the AT2 gene-deleted mice than the control, which was completely abolished by AT1 antagonist losartan. The aortic content of AT1 receptor was significantly increased (P < 0.05, n = 5) in the AT2 null mice (212 +/- 58.2 fmol/mg protein) compared with the control (98.2 +/- 55.9 fmol/mg protein). While both AT1 and AT2 mRNAs were expressed in the aorta of the control mice, only AT1 mRNA was expressed in the AT2 knockout mice. The expression of AT1 mRNA in the AT2 knockout mice was significantly higher (1.5-fold, P < 0.05, n = 5) than that in the control. The present study clearly demonstrated that the increased vascular reactivity to Ang II in AT2 knockout mice is at least partly due to an increased vascular AT1 receptor expression and suggested that AT2 counteracts AT1-mediated vascular action of Ang II through downregulation of AT1 receptor by a crosstalk between these receptors by some as yet unknown mechanisms.