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

LIU Xuan-Xuan¹, CHEN Ai-Dong^1,2, PAN Yan³, ZHANG Feng^1,2, QI Zhen-Bao⁴, CAO Nan¹, HAN Ying^1,2,*

¹Department of Physiology, Kangda College of Nanjing Medical University, Lianyungang 222000, China；²Department of Physiology, Nanjing Medical University, Nanjing 211166, China；³Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng 224005, China；⁴Engineering Training Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250000, China

Abstract

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.

Key words: angiotensin-(1-7)

Received: 　　Accepted:

Corresponding author: 韩莹　　E-mail: yhancn@njmu.edu.cn

Citing This Article：

LIU Xuan-Xuan, CHEN Ai-Dong, PAN Yan, ZHANG Feng, QI Zhen-Bao, CAO Nan, HAN Ying. Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension. Acta Physiol Sin 2023; 75 (4): 497-502 (in Chinese with English abstract).