title: Chronic ethanol ingestion increases superoxide production and NADPH oxidase expression in the lung.
abstract: Alcohol abuse increases the incidence of 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 after 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 wk. Selected animals were also treated with lisinopril (3 mg/liter) for 6 wk. 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.
authors.affiliation: Department of Medicine, Atlanta VA and Emory University Medical Center, Atlanta VAMC (151-P), 1670 Clairmont Rd., Decatur, GA 30033, USA. jpolika@emory.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Polikandriotis
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rupnow
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Elms
authors.forename: Roza E
authors.initials: RE
authors.lastname: Clempus
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Roy L
authors.initials: RL
authors.lastname: Sutliff
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
authors.forename: David M
authors.initials: DM
authors.lastname: Guidot
authors.forename: C Michael
authors.initials: CM
authors.lastname: Hart
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D019803:Glutathione Disulfide / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D013481:Superoxides; D000804:Angiotensin II; D000431:Ethanol; D017706:Lisinopril; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D007703:Peptidyl-Dipeptidase A; D019803:Glutathione Disulfide