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ORIGINAL RESEARCH article

Front. Med.
Sec. Pulmonary Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1521729
This article is part of the Research Topic Targeting Pulmonary Endothelium in Acute Lung Injury and Acute Respiratory Distress Syndrome View all 4 articles

Inhibition of Renin-Angiotensin System Attenuates Type I Alveolar Epithelial Cell Necroptosis in Rats after Hyperbaric Hyperoxic Exposure

Provisionally accepted
Wenwu Liu Wenwu Liu 1*Cuihong Han Cuihong Han 2Ying Liu Ying Liu 3Peixin Zhang Peixin Zhang 2Shifeng Wang Shifeng Wang 1
  • 1 Naval Medical Center, Shanghai, China
  • 2 Jining First People's Hospital, Jining, Shandong, China
  • 3 Yantaishan Hospital, Yantai, Shandong Province, China

The final, formatted version of the article will be published soon.

    Objective: There is evidence showing both necroptosis and activation of reninangiotensin system (RAS) are involved in the pathogenesis of hyperbaric hyperoxic lung injury (HLI). This study aimed to investigate whether RAS activation can induce lung cell necroptosis and the cell specificity of necroptosis in the lung in case of hyperbaric HLI.Methods: Male SD rats were randomly assigned into control group (n=12), HLI group (n=18), captopril group (n=18), and valsartan group (n=18). Rats were pretreated with intraperitoneal captopril (50 mg/kg) or intragastrical valsartan (30 mg/kg) for 3 days before hyperbaric exposure. Then, animals were exposed to 99.9% oxygen at 250 kPa for 6 h to induce HLI. After hyperbaric exposure, lung function was noninvasively detected, and then animals were sacrificed for the detection of wet to dry ratio of the lung, blood gas and lung inflammatory factors, and lung tissues were collected for double immunofluorescence staining. Statistical analysis was performed with one way analysis of variance.Results: Either valsartan or captopril pre-treatment could inhibit lung edema, improve blood gas (0 h) and lung function (48 h), and reduce pro-inflammatory factors in the lung. In addition, valsartan or captopril pre-treatment could inhibit AGTR1 expression and lung cell necroptosis, and type I alveolar epithelial cells (AECs) were the major cell type experiencing necroptosis after hyperbaric hyperoxic exposure.Our study indicates inhibition of RAS can suppress the hyperbaric HLI, which may be, at least partially, related to the inhibition of type I AECs necroptosis.Our findings provide new mechanism for the protective effects of RAS inhibition on hyperbaric HLI.

    Keywords: hyperbaric hyperoxic lung injury, necroptosis, Renin-Angiotensin System, type I alveolar epithelial cells, Inflammation

    Received: 02 Nov 2024; Accepted: 27 Jan 2025.

    Copyright: © 2025 Liu, Han, Liu, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wenwu Liu, Naval Medical Center, Shanghai, 200052, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.