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

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.

• Authors: Xuan-Xuan Liu, Ai-Dong Chen, Yan Pan, Feng Zhang, Zhen-Bao Qi, Nan Cao, Ying Han
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 75 Issue 4 Pg. 497-502 (Aug 25 2023) ISSN: 0371-0874 [Print] China
• PMID: 37583036 (Publication Type: English Abstract, Journal Article)

Chemical References

• Monocrotaline
• angiotensin I (1-7)
• Acetylcholine
• Nitroprusside

Topics

• Rats
• Humans
• Animals
• Vasodilation
• Pulmonary Arterial Hypertension
• Monocrotaline (toxicity)
• Rats, Sprague-Dawley
• Hypertension, Pulmonary (chemically induced)
• Endothelial Cells
• Pulmonary Artery
• Endothelium
• Acetylcholine (pharmacology)
• Nitroprusside (pharmacology)