Nitrogen dioxide causes pulmonary arterial relaxation via thiol
nitrosation and no formation.
Davidson, Cathleen A., Pawel M. Kaminski, Mingdan Wu, and Michael S.
Wolin.
Departments of Physiology and Experimental Pathology, New York
Medical College, Valhalla, NY. 10595
APStracts 2:0385H, 1995.
Micromolar concentrations of nitrogen dioxide (NO2), a key metabolite
of nitric oxide (NO) and peroxynitrite (ONOO-), were observed to
cause a prolonged relaxation of isolated endothelium-removed rings of
bovine pulmonary arteries (BPA) precontracted with 30 mM potassium.
Relaxation to NO2 was markedly inhibited by 1 [mu]M oxyhemoglobin
(Hb), 10 [mu]M methylene blue (MB) and 10 [mu]M LY83583. The response
to NO2 was enhanced in the presence of 1 mM glutathione (GSH) or
cysteine. The addition of NO2 to Krebs bicarbonate (under 95% N2-5%
CO2) containing 1 mM GSH or BPA resulted in an increase in NO
formation (measured in head space gas). Relaxation to NO2 and NO
formation were markedly decreased after GSH depletion by pretreatment
of BPA with diethylmaleate. A HPLC analysis of the products formed
immediately after the addition of NO2 to GSH detected a previously
isolated (but not identified) potent relaxing agent formed by a
reaction of GSH with ONOO-, and this material comigrated with a
synthetic product thought to be S-nitro-GSH (GSNO2). Nanomolar
concentrations of GSNO2 caused a potent dose-dependent relaxation
that was inhibited by Hb, MB and LY83583. Therefore, NO2 appears to
cause a prolonged cGMP-mediated relaxation in BPA via thiol nitration
and a subsequent time-dependent release of NO. Thus, NO2 (and ONOO-)
may function in a tissue hormone-like regulatory role in inflammatory
processes where large amounts of these species are produced.
Received 12 June 1995; accepted in final form 23 August 1995.
APS Manuscript Number H530-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.