Intrapulmonary Activation of the Angiotensin-Converting Enzyme Type 2/Angiotensin 1-7/G-Protein-Coupled Mas Receptor Axis Attenuates Pulmonary Hypertension in Ren-2 Transgenic Rats Exposed to Chronic Hypoxia
Intrapulmonary Activation of the Angiotensin-Converting Enzyme Type 2/Angiotensin 1-7/G-Protein-Coupled Mas Receptor Axis Attenuates Pulmonary Hypertension in Ren-2 Transgenic Rats Exposed to Chronic Hypoxia
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DOI：
10.33549/physiolres.932861
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Cervenka, L.
中科院分区：
文献类型：
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作者：
Hampl, V.;Herget, J.;Cervenka, L.
本研究旨在评价肺内活动的两个轴的肾素-血管紧张素系统（RAS）的作用：血管收缩剂血管紧张素转换酶（ACE）/血管紧张素II（ANG II）/ANG II 1型受体（AT 1）轴和血管扩张剂ACE 2型（ACE 2）/血管紧张素1-7（ANG 1-7）/Mas受体轴，在Ren-2转基因大鼠（TGR）缺氧性肺动脉高压的形成中的作用。转基因阴性汉诺威Sprague-Dawley（HanSD）大鼠作为对照。TGR和HanSD大鼠对两周的低氧暴露均表现出显著的平均肺动脉压（MPAP）升高，但前者的升高程度较低。与HanSD大鼠相比，TGR大鼠缺氧性肺动脉高压的减轻与肺组织中ACE基因表达和活性的抑制、AT 1受体基因表达的抑制和ANG II水平的抑制有关。同时，肺ACE 2基因表达和活性增加，特别是ANG 1-7浓度和Mas受体基因表达增加。提示肺组织RAS的ACE/ANG Ⅱ/AT 1受体轴抑制和ACE 2/ANG 1-7/Mas受体轴激活是TGR大鼠低氧性肺动脉高压减轻的主要机制。
The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT1) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks' exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT1 receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT1 receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.