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.
Sheng Li Xue Bao. 2023 Aug 25;75(4):497-502.
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 × 10-1 × 10 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.
在本研究中，我们使用由野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠模型来研究血管紧张素（Ang）-(1-7)在调节肺动脉舒张功能中的作用及机制。皮下注射MCT或生理盐水三周后，使用右心导管检测大鼠的右心室收缩压（RVSP）和右心室肥厚指数（RVHI）。通过乙酰胆碱（ACh）诱导的血管舒张来评估血管内皮依赖性舒张功能。通过硝普钠（SNP）诱导的血管舒张来评估血管平滑肌的舒张功能。将人肺动脉内皮细胞（HPAECs）与Ang-(1-7)孵育以测量一氧化氮（NO）释放水平。结果显示，与对照大鼠相比，MCT-PAH大鼠的RVSP和RVHI显著升高，并且ACh或SNP诱导的血管舒张均恶化。用Ang-(1-7)（1×10 - 1×10 mol/L）孵育MCT-PAH大鼠的肺动脉可引起显著的血管舒张。在MCT-PAH大鼠的肺动脉中预先孵育Ang-(1-7)可显著改善ACh诱导的内皮依赖性舒张，但对SNP诱导的非内皮依赖性舒张无显著影响。此外，Ang-(1-7)处理显著增加了HPAECs中的NO水平。Mas受体拮抗剂A-779抑制了Ang-(1-7)对内皮依赖性舒张和内皮细胞NO释放的作用。上述结果表明，Ang-(1-7)通过激活Mas受体促进内皮细胞释放NO，从而改善PAH肺动脉的内皮依赖性舒张功能。
