血管紧张素-(1-7)改善野百合碱诱导的肺动脉高压大鼠内皮依赖性血管舒张  

Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension

作　　者：刘宣宣[1] 陈艾东 潘艳[3] 张枫 綦振宝 曹囡[1] 韩莹 LIU Xuan-Xuan;CHEN Ai-Dong;PAN Yan;ZHANG Feng;QI Zhen-Bao;CAO Nan;HAN Ying(Department of Physiology,Kangda College of Nanjing Medical University,Lianyungang 222000,China;Department of Physiology.Nanjing Medical University,Nanjing 211166,China;Department of Basic Medicine,Jiangsu Vocational College of Medicine,Yancheng 224005,China;Engineering Training Center,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250000,China)

机构地区：[1]南京医科大学康达学院生理学教研室,连云港222000 [2]南京医科大学生理学系,南京211166 [3]江苏医药职业学院基础医学部,盐城224005 [4]齐鲁工业大学(山东省科学院)工程训练中心,济南250000

出　　处：《生理学报》2023年第4期497-502,共6页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 82270455);the Natural Science Foundation of Jiangsu Higher Education Institutions of China (No. 22KJD180003);the Natural Science Foundation of Jiangsu Vocational College of Medicine,China (No. 20214104)。

摘　　要：本研究采用野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠模型,旨在探讨血管紧张素(angiotensin,Ang)-(1-7)在调控PAH大鼠肺动脉舒张功能中的作用及机制。皮下注射MCT或生理盐水3周后用右心导管检测大鼠右心室收缩压(right ventricular systolic pressure,RVSP)和右心肥厚指数(right ventricular hypertrophy index,RVHI)来鉴定PAH模型。通过肺动脉等长张力实验评价血管舒张功能,应用乙酰胆碱(acetylcholine,ACh)诱导的血管舒张评价血管内皮依赖性舒张功能,应用硝普钠(sodium nitroprusside,SNP)诱导的血管舒张评价血管平滑肌舒张功能。Ang-(1-7)孵育人肺动脉内皮细胞(human pulmonary artery endothelial cells,HPAECs)测定一氧化氮(nitric oxide,NO)释放水平。结果显示:与对照大鼠相比,MCT-PAH大鼠RVSP和RVHI明显升高,ACh或SNP诱导的血管舒张功能均变差。采用1×10^(-9)~1×10^(-4) mol/L Ang-(1-7)孵育MCT-PAH大鼠离体肺动脉血管环,引起明显的肺动脉舒张。MCT-PAH大鼠肺动脉孵育Ang-(1-7)预处理后,明显改善ACh诱导的血管内皮依赖性舒张,但对SNP诱导的血管内皮非依赖性舒张无明显作用。Ang-(1-7)孵育HPAECs明显升高其释放的NO水平。Mas受体拮抗剂A-779抑制Ang-(1-7)的改善ACh诱导的血管舒张功能、促进内皮细胞NO释放作用。上述结果表明,Ang-(1-7)通过激活Mas受体促使内皮细胞释放NO,改善PAH大鼠肺动脉血管内皮依赖性舒张功能。In this study,we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function.Three weeks after subcutaneous injection of MCT or normal saline,the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter.Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation.The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation.Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels.The results showed that compared with control rats,RVSP and RVHI were significantly increased in the MCT-PAH rats,and both ACh or SNP-induced vasodilation were worsened.Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7)(1×10^(-9)–1×10^(-4) mol/L) caused significant vaso-relaxation.Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation,but had no significant effect on SNP-induced endothelium-independent relaxation.In addition,Ang-(1-7) treatment significantly increased NO levels in HPAECs.The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells.The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor,thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.

关 键 词：血管紧张素-(1-7) 肺动脉高压 内皮依赖性舒张功能 一氧化氮 MAS受体 

分 类 号：R544.1[医药卫生—心血管疾病]