Published ahead of print on November 11, 2005, doi:10.1165/rcmb.2005-0320OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 3, March 2006, 314-319 A more recent version of this article appeared on March 1, 2006
Submitted on August 22, 2005 Chronic Ethanol Ingestion Increases Superoxide Production and NADPH Oxidase Expression in the LungJohn A Polikandriotis1*,1 Department of Medicine, Atlanta Veterans Affairs Medical Center and Emory University, Atlanta, GA, USA, 2 St. Vincent's Institute of Medical Research and the Department of Medicine, University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, Australia, 3 Department of Pediatrics and Biochemistry, Emory Univeristy, Atlanta, GA, USA * To whom correspondence should be addressed. E-mail: jpolika{at}emory.edu.
Alcohol abuse increases the incidence of the Acute Respiratory Distress Syndrome and causes oxidative stress and cellular dysfunction in the lung. The mechanisms of ethanol (EtOH)-induced oxidative stress in the lung remain to be defined. Chronic alcohol ingestion has been associated with increased renin-angiotensin system (RAS) activity. Therefore the current study investigated the ability of lisinopril, an angiotensin converting enzyme (ACE) inhibitor, to modulate oxidative stress in the lung following chronic EtOH ingestion in a well established rat model. Male Sprague Dawley rats were fed liquid diets containing EtOH (36% of calories) or maltose-dextrin as an isocaloric substitution for EtOH (Control) for 6 weeks. Selected animals were also treated with lisinopril (3 mg/L) for 6 weeks. Chronic EtOH ingestion increased bronchoalveolar lavage fluid glutathione disulfide levels and superoxide formation in lung parenchyma. These effects of EtOH were attenuated by lisinopril treatment. Chronic EtOH ingestion failed to increase ACE expression or angiotensin II levels in lung homogenates, but increased angiotensinogen, angiotensin II type 1 and type 2 receptor levels, and ACE activity. Chronic EtOH ingestion also increased the levels of the NADPH oxidase subunit, gp91phox, an effect that was attenuated by lisinopril, but had no effect on lung p22phox or p47phox levels. These findings suggest that EtOH-mediated RAS activation plays an important role in pulmonary oxidative stress and provide new insights into mechanisms by which EtOH causes oxidative stress in the lung and potential strategies of lung protection through ACE inhibition.
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