AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 628-L634, Copyright © 1994 by American Physiological Society
Peroxynitrite inhibition of oxygen consumption and sodium transport in alveolar type II cells
P. Hu, H. Ischiropoulos, J. S. Beckman and S. Matalon
Department of Anesthesiology, University of Alabama at Birmingham 35233-1924.
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.
