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195 THE RENIN ANGIOTENSIN SYSTEM MEDIATES CHRONIC ETHANOL-INDUCED INCREASES IN SUPEROXIDE PRODUCTION AND NADPH OXIDASE EXPRESSION IN THE LUNG
  1. J. A. Polikandriots,
  2. H. L. Rupnow,
  3. R. L. Sutliff,
  4. L. S. Brown,
  5. D. M. Guidot,
  6. C. M. Hart
  1. Atlanta, GA.

Abstract

Purpose Chronic ethanol (EtOH) ingestion increases the incidence of the acute respiratory distress syndrome and causes oxidative stress and cellular dysfunction in the lung. The mechanisms of EtOH-induced oxidative stress in the lung remain to be defined. We sought to determine if chronic EtOH ingestion alters the expression of lung NADPH oxidase, a major enzymatic source of superoxide generation, in an in vivo rat model of chronic EtOH ingestion.

Methods Male Sprague-Dawley rats were fed liquid diets containing EtOH (36% of calories) or an isocaloric diet substituting maltin-dextrin for EtOH (control) with or without the angiotensin-converting enzyme (ACE) inhibitor lisinopril for 6 weeks. Prior to sacrifice, blood pressure was monitored for 15-20 minutes. After sacrifice, lung frozen sections were stained with dihydroethidium (DHE) to detect superoxide production. Expression of specific components of the renin-angiotensin system (RAS) and specific NADPH oxidase components were then examined in lung homogenates.

Results Chronic EtOH ingestion in the rat had no significant effect on blood pressure but increased superoxide formation in lung parenchyma measured as DHE fluorescence, an effect inhibited by lisinopril. Chronic EtOH ingestion failed to increase lung ACE expression, but increased angiotensinogen, angiotensin II type 1 (AT1) and type 2 (AT2) receptor expression. Chronic EtOH ingestion also increased expression of the NADPH oxidase subunit, gp91phox, an effect inhibited by lisinopril.

Conclusions These results indicate that chronic EtOH ingestion alters superoxide production and specific NADPH oxidase subunit expression in the lung by a RAS-dependent pathway. These findings provide new insights into mechanisms by which EtOH causes oxidative stress in the lung.

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