Nitric oxide alters metabolism in isolated alveolar type ii
cells.
Miles, P. R., L. Bowman, and L. Huffman.
Division of Respiratory Disease Studies, National Institute for
Occupational Safety and Health, Morgantown, WV 26505 and Department
of Physiology, West Virginia University School of Medicine,
Morgantown, WV 26506
APStracts 3:0030L, 1996.
Alveolar type II cells may be exposed to nitric oxide ( x NO) from
external sources and these cells can also generate x NO. Therefore,
we studied the effects of altering x NO levels on various type II
cell metabolic process. Incubation of cells with the x NO generator,
S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of
60-70% in the synthesis of disaturated phosphatidylcholines (DSPC)
and cell ATP levels. Cellular oxygen consumption, an indirect measure
of cell ATP synthesis, is also reduced by SNAP. There is no direct
effect of SNAP on lung mitochondrial ATP synthesis, suggesting that x
NO does not directly inhibit this process. On the other hand,
incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME),
an inhibitor of the enzyme responsible for x NO synthesis (nitric
oxide synthase; NOS), results in increases in DSPC synthesis, cell
ATP content, and cellular oxygen consumption. The L-NAME effects are
reversed by addition of L-arginine, the substrate for NOS. Production
of x NO by type II cells is inhibited by L-NAME, a better inhibitor
of constituitive NOS (cNOS) than inducible NOS (iNOS), and is reduced
in the absence of external calcium. Aminoguanidine, a specific
inhibitor of iNOS, has no effect on cell ATP content or on x NO
production. These results indicate that alveolar type II cell lipid
and energy metabolism can be affected by x NO and suggest that there
may be cNOS activity in these cells.
Received 21 June 1995; accepted in final form 26 January 1996.
APS Manuscript Number L195-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96