Peroxynitrite inhibition of oxygen consumption and sodium transport in alveolar type II cells.
Active sodium (Na+) transport by alveolar type II (ATII) cells plays an important role in limiting the volume of alveolar fluid. Reactive oxygen and nitrogen species, released in the epithelial lining fluid by activated inflammatory cells or present in inspired gases, may damage Na+ transporters and decrease fluid reabsorption. To test this hypothesis we exposed ATII cells to xanthine and xanthine oxidase (1 or 10 mU/ml), or to boluses of peroxynitrite (0.1-1 mM final concentration) for 15 min and measured 1) cellular oxygen consumption (VO2); 2) amiloride-inhibitable 22Na+ uptake, as an index of Na+ movement through apically located Na+ channels; and 3) ouabain-sensitive 86Rb+ uptake, as an index of the activity of the basolaterally located Na(+)-K(+)-ATPase. After exposure of ATII cells to 0.5 or 1 mM peroxynitrite, amiloride-inhibitable 22Na+ uptake decreased to 68 +/- 7 and 56 +/- 11 of their control values, respectively (mean +/- SE; n > or = 6). Exposure to 0.5 mM peroxynitrite decreased ATII cell VO2 from 76 +/- 6 to 25 +/- 5 microM.h-1 x 10(6) cells-1 (mean +/- SE; n = 5). Cell viability and ouabain-sensitive 86Rb+ uptake remained at control levels for either peroxynitrite concentration. Exposure of ATII cells to 10 mU/ml xanthine oxidase decreased their VO2 from 94 +/- 8 to 63 +/- 6 (mean +/- SE; n = 5), but did not alter amiloride-inhibitable 22Na+ uptake. These findings indicate that physiological concentrations of peroxynitrite, but not of reactive oxygen species, decrease ATII cell Na+ transport by damaging apically located amiloride-sensitive Na+ channels.
Department of Anesthesiology, University of Alabama at Birmingham 35233-1924.
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Hu
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Ischiropoulos
J S
JS
Beckman
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Matalon
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D005290:Ferric Compounds; D009566:Nitrates; D017382:Reactive Oxygen Species; D014970:Xanthines; D019820:Xanthine; C039642:peroxynitric acid; D010042:Ouabain; D000584:Amiloride; D004492:Edetic Acid; D012964:Sodium; D014969:Xanthine Oxidase; C019179:Fe(III)-EDTA; D012413:Rubidium