Wei Tao1, Ping-Song Li2, Gang Xu2, Yi Luo2, Yu-Sheng Shu3, Yong-Zhong Tao4, Liu-Qing Yang4. 1. Department of Surgery, Subei People's Hospital of Jiangsu Province, Jiangsu, China. 2. Department of Burn and Plastic Surgery, Subei People's Hospital of Jiangsu Province, Jiangsu, China. 3. Department of Thoracic Surgery, Subei People's Hospital of Jiangsu Province, Jiangsu, China. 4. Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Jiangsu, China.
Abstract
BACKGROUND: Angiotensin II plays a vital role in the pathogenesis of acute respiratory distress syndrome (ARDS). However, its mechanism is not well defined. Angiotensin II upregulates the expression of soluble epoxide hydrolase (sEH; Ephx2). sEH is suggested as a potential pharmacologic target for ARDS. The present study investigates whether the sEH is involved in the angiotensin II-triggered pulmonary inflammation and edema using an angiotensin II-induced lung injury animal model. METHODS: Lung injury was induced by angiotensin II intratracheally instillation in wild-type or Ephx2 deficient mice. RESULTS: sEH activities were markedly increased in wild-type mice treated with angiotensin II. Angiotensin II markedly increased the levels of tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid, worsened alveolar capillary protein leak and lung histological alterations, and elevated activity of activator protein-1 and nuclear factor-κB. However, these changes were significantly improved in Ephx2 deficient mice. Moreover, Losartan, an angiotensin II receptor 1 antagonist, abolished the sEH induction and improved mortality. CONCLUSIONS: Angiotensin II-induced lung injury was improved in sEH gene deleted mice. The angiotensin II-triggered pulmonary inflammation is mediated, at least in part, through the sEH.
BACKGROUND: Angiotensin II plays a vital role in the pathogenesis of acute respiratory distress syndrome (ARDS). However, its mechanism is not well defined. Angiotensin II upregulates the expression of soluble epoxide hydrolase (sEH; Ephx2). sEH is suggested as a potential pharmacologic target for ARDS. The present study investigates whether the sEH is involved in the angiotensin II-triggered pulmonary inflammation and edema using an angiotensin II-induced lung injury animal model. METHODS:Lung injury was induced by angiotensin II intratracheally instillation in wild-type or Ephx2 deficient mice. RESULTS:sEH activities were markedly increased in wild-type mice treated with angiotensin II. Angiotensin II markedly increased the levels of tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid, worsened alveolar capillary protein leak and lung histological alterations, and elevated activity of activator protein-1 and nuclear factor-κB. However, these changes were significantly improved in Ephx2 deficient mice. Moreover, Losartan, an angiotensin II receptor 1 antagonist, abolished the sEH induction and improved mortality. CONCLUSIONS: Angiotensin II-induced lung injury was improved in sEH gene deleted mice. The angiotensin II-triggered pulmonary inflammation is mediated, at least in part, through the sEH.
Authors: Nicholas E Ingraham; Abdo G Barakat; Ronald Reilkoff; Tamara Bezdicek; Timothy Schacker; Jeffrey G Chipman; Christopher J Tignanelli; Michael A Puskarich Journal: Eur Respir J Date: 2020-07-09 Impact factor: 16.671