Objective To investigate the role of angiotensin-II type 1 receptor ( AT1) antagonist in treatment of acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods Animal model of ALI/ARDS was induced by cecal ligation and perforation ( CLP) . ALI/ARDS animals received a separate intraperitoneal injection of several concentrations( 5, 10, 15, 20, 25 mg/kg) of AT1 inhibitor losartan after CLP, then the changes of lung injury and 7-day survival were measured. Results Oxygenation index and lung wet to dry weight ratio ( W/D) showed an improving trend when losartan was administered at doses of 5 to 15 mg/kg in ALI/ARDS rats, but aggravated above the dose of 15 mg/kg. Losartan ( 15 mg/kg) treatment significantly alleviated pulmonary edema after CLP operation, and decreased serumlevels of TNF-α, IL-6, and
IL-1β [ TNF-α: ( 554. 1 ±62. 7 ) pg/mL vs. ( 759. 2 ±21. 5 ) pg/mL, P lt; 0. 01; IL-6: ( 1227. 3 ±130. 0) pg/mL vs. ( 2670. 4 ±174. 1) pg/mL, P lt; 0. 01; IL-1β: ( 444. 0 ±38. 6) pg/mL vs. ( 486. 6 ±61. 7)pg/mL, P lt; 0. 05] . 7-day survival rate also increased in losartan treatment group at a dose of 15 mg/kg( 6. 7% vs. 0 ) . Conclusions The AT1 inhibitor, losartan, can significantly prevent lung injury in ALI/ARDS after CLP, and improve the 7-day survival rate.
Citation：
SHEN Lihan,MO Hongying,CAI Lihua,QIN Bingjun,XIAO Zhenglun.. Losartan Alleviates Lung Inflammation of Rats with Acute Lung Injury. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(4): 409-412. doi:
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Copyright © the editorial department of Chinese Journal of Respiratory and Critical Care Medicine of West China Medical Publisher. All rights reserved
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- 1. 沈利汉, 莫红缨, 蔡立华, 等. 肾素-血管紧张素系统与ALI/ARDS 的关系探讨. 中国呼吸与危重监护杂志, 2010, 9: 310 -314.
- 2. Singleton KD, Beckey VE, Wischmeyer PE. Glutamine prevents activation of NF-KB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome ( ARDS) following sepsis. Shock, 2005 , 24, 583 -589.
- 3. Ruiz-Ortega M, Esteban V, Rupérez M, et al. Renal and vascular hypertension-induced inflammation: role of angiotensin II. Curr Opin Nephrol Hypertens, 2006 , 15: 159-166.
- 4. He X, Han B,Mura M, et al. Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats.Shock, 2007 , 28 : 106-111.
- 5. Jerng JS, Hsu YC, Wu HD, et al. Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model.Thorax, 2007, 62: 527-535.
- 6. Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review.Intern Med, 2009 , 48: 621-630.
- 7. Bedirli A, Kerem M, Pasaoglu H, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock, 2007, 27: 397-401 .
- 8. Meduri GU. Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome. Crit Care, 2002, 6: 24-29.
- 9. Yeh CC, Kao SJ, Lin CC, et al. The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci,2007, 80: 1821-1831.
