Potential role of nadh oxidoreductase-derived reactive o2 species
in calf pulmonary arterial po2-elicited responses.
Mohazzab-H., Kamal M., Raisa P. Fayngersh, Pawel M. Kaminski, and
Michael S. Wolin.
Department of Physiology, New York Medical College, Valhalla, NY.
10595
APStracts 2:0104L, 1995.
Our laboratory has previously reported evidence that tone responses of
isolated endothelium-removed calf pulmonary arteries elicited by
changes in PO2 appear to be mediated via changes in H2O2 and cGMP,
and that the PO2 sensor mechanism is hypothesized to involve changes
in superoxide anion (O2.-) production by a microsomal NADH
-oxidoreductase, which is the major source of O2.- in this tissue
detected by lucigenin-elicited chemiluminescence (CL). In this study
we examined if the flavoprotein-directed inhibitor of O2.- producing
NAD(P)H oxidoreductases, diphenyliodonium (DPI), could be employed as
an inhibitor of O2.- production by NADH oxidoreductase which
functions as a selective probe for PO2-elicited tone responses in
calf pulmonary arterial smooth muscle. It was found that 1 [mu]M DPI
inhibited NADH-dependent production of CL in the arterial smooth
muscle homogenate by 49% (n=10). DPI reduced basal CL from
endothelium-removed pulmonary arteries by 41% (n=15). In endothelium
-removed pulmonary arteries precontracted with U46619, the hypoxic
contraction of 2.3+/-0.5 g was reduced to 0.1+/-0.4 g (n=7) by DPI
and the reoxygenation relaxation of 32.7+/-7.5% was decreased to
4.4+/-1.4% (n=7). DPI did not have any significant effect on U46619
or K- elicited tone generation. DPI also did not alter the relaxation
to H2O2 (1 [mu]M-0.1 mM n=6), nitric oxide (0.42 nM-420 nM, n=12) or
isoproterenol (1 nM-1 [mu]M, n=6). Probes for other flavoprotein O2.-
producing systems, including xanthine oxidase (0.1 mM oxypurinol),
nitric oxide synthase (0.1 mM nitro-L-arginine) or mitochondrial
electron transport (50 [mu]M rotenone) did not alter the tone
response to changes in PO2. These results are consistent with a
hypothesized role for H2O2 formation via NADH oxidoreductase-derived
O2.- in pulmonary artery responses to changes in PO2.
Received 19 August 1994; accepted in final form 13 June 1995.
APS Manuscript Number L242-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.