Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice.

Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice.
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AT(2) 受体基因破坏小鼠肾小球中 AT(1) 受体表达和 mRNA 增加。

DOI:
10.1152/ajprenal.2001.280.1.f71
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发表时间:
2001
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Armando,I
Armando,I
中科院分区:
--
文献类型:
--
作者:
Saavedra,JM;Hauser,W;Ciuffo,G;Egidy,G;Hoe,KL;Johren,O;Sembonmatsu,T;Inagami,T;Armando,I

文献摘要

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血管紧张素II AT 2和AT 1受体之间的反馈提示我们研究雄性AT 2受体基因破坏小鼠(agtr 2 −/y)肾脏中AT 1受体的表达。在野生型(agtr 2 +/y)小鼠中,AT 1受体结合和mRNA在肾小球中是丰富的,并且AT 1受体结合在外髓质的内部条纹中也是高的。AT 2受体很少,主要与皮质血管结构相关。在Inagtr 2 −/y小鼠中,肾小球中的AT 1受体结合和mRNA增加,其余皮质和外髓质的外条纹中的AT 1受体结合更高,但其内条纹中没有,表明不同的细胞调节。虽然在maleagtr 2+/y小鼠中AT 2受体表达非常低,但它们的基因破坏改变了AT 1受体表达。单独的AT 1上调可以解释AT 2基因破坏小鼠的表型,如血压升高,对血管紧张素II的敏感性增加,肾功能改变。由于AT 1受体拮抗剂在临床上的广泛应用,AT 1/AT 2受体间接反馈可能具有临床意义。
The proposed feedback between angiotensin II AT2and AT1receptors prompted us to study AT1receptor expression in kidneys of male AT2receptor-gene disrupted mice (agtr2−/y). In wild-type (agtr2+/y) mice, AT1receptor binding and mRNA is abundant in glomeruli, and AT1receptor binding is also high in the inner stripe of the outer medulla. AT2receptors are scarce, primarily associated to cortical vascular structures. Inagtr2−/y mice, AT1receptor binding and mRNA were increased in the kidney glomeruli, and AT1receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT2receptor expression is very low in maleagtr 2+/y mice, their gene disruption alters AT1receptor expression. AT1upregulation alone may explain the AT2gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT1/AT2receptor feedback could have clinical significance because AT1antagonists are widely used in medical practice.