AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 6 823-L831, Copyright © 1994 by American Physiological Society
Properties of a superoxide anion-generating microsomal NADH oxidoreductase, a potential pulmonary artery PO2 sensor
K. M. Mohazzab and M. S. Wolin
Department of Physiology, New York Medical College, Valhalla 10595.
In this study, we describe properties of a microsomal NADH oxidoreductase
that is a potential PO2-dependent source of vasoactive reactive O2 species
in the calf pulmonary artery. Microsomes show an NADH-dependent production
of superoxide anion (O2-.), as detected by lucigenin-elicited
chemiluminescence, a superoxide dismutase inhibited reduction of nitro blue
tetrazolium (NBT) and 2,6-dichlorophenol-indophenol, and O2 consumption.
The microsomal production of O2-. was modulated by physiologically relevant
levels of NADH and PO2, and O2-. production was reduced by inhibitors of
NADH-dependent microsomal electron transport. Microsomes catalyzed an
NADH-mediated reduction of several electron acceptor dyes, cytochrome c
(rotenone insensitive) and methemoglobin. On reduction with dithionite, a
cytochrome with an absorbance at approximately 558 nm was observed.
Arterial O2-. levels (chemiluminescence) were also reduced by NBT and
microsomal electron transport inhibitors. In pulmonary arteries, NBT
selectively inhibited PO2 and lactate elicited changes in force generation,
presumably by trapping O2-. and preventing H2O2 formation. Thus these
studies are consistent with an involvement of O2-.-derived H2O2 generation
via a microsomal NADH-cytochrome b558 electron transport system in calf
pulmonary artery smooth muscle PO2 and lactate-elicited tone responses.
