Renal proximal tubule angiotensin AT1A receptors regulate blood pressure
Renal proximal tubule angiotensin AT1A receptors regulate blood pressure
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DOI：
10.1152/ajpregu.00124.2011
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发表时间：
2011-10-01
影响因子：
2.8
通讯作者：
Sigmund, Curt D.
中科院分区：
文献类型：
--
作者：
Li, Huiping;Weatherford, Eric T.;Sigmund, Curt D.
Li H，Weatherford ET，Davis DR，Keen HL，Grobe JL，Daughtera A，Coconut LA，艾伦AM，Sigmund CD.肾近曲小管血管紧张素AT 1A受体调节血压。Am J Physiol Regul Integr Comp Physiol 301：R1067-R1077，2011年。首次发表于2011年7月13日; doi：10.1152/ajpregu.00124.2011。据报道，血管紧张素II生成和作用所必需的肾素血管紧张素系统的所有组分都存在于肾近曲小管中。考虑到肾钠处理和血压调节之间的密切关系，我们假设调节血管紧张素II在肾近端小管中的作用将改变慢性血压水平。为了测试这一点，我们使用了近端小管特异性，雄激素依赖性，启动子构建体（KAP 2），以产生过度表达的组成型活性血管紧张素1A型受体转基因或内源性血管紧张素1A型受体耗尽的小鼠。雄激素给药雌性转基因小鼠引起肾脏中转基因的强烈诱导和基线血压升高。在受体缺失的小鼠中，给予雌性雄激素导致近端小管中Cre重组酶介导的血管紧张素1A型受体缺失，并降低血压。与基线时观察到的变化相反，在两种实验模型中，对升压剂量的ANG II的血压反应没有差异。来自两个独立小鼠模型的这些数据提供了证据，表明在基线条件下，通过肾近端小管中的1A型受体的ANG II信号传导是全身血压的调节剂。
Li H, Weatherford ET, Davis DR, Keen HL, Grobe JL, Daugherty A, Cassis LA, Allen AM, Sigmund CD. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure. Am J Physiol Regul Integr Comp Physiol 301: R1067-R1077, 2011. First published July 13, 2011; doi:10.1152/ajpregu.00124.2011.-All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to generate mice with either overexpression of a constitutively active angiotensin type 1A receptor transgene or depletion of endogenous angiotensin type 1A receptors. Androgen administration to female transgenic mice caused a robust induction of the transgene in the kidney and increased baseline blood pressure. In the receptor-depleted mice, androgen administration to females resulted in a Cre recombinase- mediated deletion of angiotensin type 1A receptors in the proximal tubule and reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of ANG II in either experimental model. These data, from two separate mouse models, provide evidence that ANG II signaling via the type 1A receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions.