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洛萨坦和代谢物EXP3179在AT2受体KO小鼠中激活内皮功能而不会降低血压

Elodie Sauge¹, Zoe White¹, Farah Lizotte²

¹Department of Anesthesiology, Pharmacology & Therapeutics, D Department of Chemistry, University of British Columbia (UBC), Vancouver, Canada; Centre for Heart Lung Innovation, University of British Columbia (UBC), Vancouver, Canada.

European journal of pharmacology

|May 30, 2024

概括

像洛萨坦这样的 ангиотензинII受体阻断剂 (ARBs) 通过氧化和EDHF释放来增强内皮功能,独立于经典的AT1/AT2通路. 这解释了ARBs除了降低血压之外的类保护作用.

科学领域:

心血管药理学心血管药理学
内皮细胞功能内皮细胞功能
接收器信号传输接收器信号传输

背景情况:

ангиотензинII受体阻断剂 (ARBs) 具有性作用,包括氧化物 (NO) 和内皮衍生的高极化因子 (EDHF) 释放,可能有助于它们的保护性质.
通过ARB降低血压 (BP) 可能涉及从 ангиотензинII受体1 (AT1) 转移到 ангиотензинII受体2 (AT2) 信号,从而刺激内皮NO释放.

研究的目的:

研究AT1和AT2受体在调解洛萨坦及其代谢物EXP3179.9内皮功能激活性质方面的不同作用.
为了确定洛萨坦和EXP3179的内皮作用是否依赖于正规的 ангиотензинII (ANGII) /AT1/AT2信号轴.

主要方法:

利用AT1受体阻塞和AT2-null小鼠评估EXP3179和洛萨坦对内皮功能,血压和大动脉硬的外体和体内影响.
长期在体内使用EXP3179 (20μM) 活体和洛萨坦 (0.6 g/l).

主要成果:

活体外,AT1受体阻塞并没有抑制EXP3179对NO和EDHF依赖性内皮功能的激活.
EXP3179在野生型 (WT) 和AT2淘汰 (KO) 甲状腺环中减少了烯诱导的收缩性.
慢性洛萨坦治疗在体内显著减少了WT和AT2KO小鼠的烯诱导的收缩,但AT2的存在对降低血压至关重要.

结论:

洛萨坦和EXP3179的内皮功能增强作用在很大程度上独立于经典的ANGII/AT1/AT2通路.
这种独立性揭示了ARBs除了降血压效果之外的类机理.

关键词:

AT1 AT1 的时间在AT2中,它是AT2.ангиотензин II 的使用.血压血压血压血压脑内皮质 (Endothelium) 是一个内皮质.洛萨坦洛萨坦洛萨坦

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