Nitric oxide inhibits pulmonary artery catalase and h2o2-associated
relaxation.
Mohazzab-H., Kamal M., Raisa P. Fayngersh, and Michael S. Wolin.
Department of Physiology, New York Medical College, Valhalla, NY
10595
APStracts 3:0180H, 1996.
Our previous studies on the mechanism of relaxation of calf pulmonary
arteries to hydrogen peroxide (H2O2) detected a role for increased
formation of guanosine-3',5'-cyclic monophosphate (cGMP) as a result
of a catalase-elicited activation of soluble guanylate cyclase. We
have also shown that lactate elicits relaxation through increasing
H2O2 produced from NADH oxidase-derived superoxide anion (O2.-).
Since nitric oxide (NO) is a potential inhibitor of catalase, we
examined the effects of exposure of endothelium-denuded bovine calf
pulmonary arteries to an elevated physiological level of NO on
relaxation to H2O2 and lactate. Treatment of pulmonary arteries with
50 nM of NO gas for 2 min caused a subsequent inhibition of
relaxation to H2O2 (10-6-10-3 M) and lactate (1-10 mM), without
markedly altering relaxation responses to S-nitroso-N
-acetylpenicillamine (SNAP, 10-9-10-6 M) or isoproterenol (10-9-10-6
M). This NO exposure caused a 63% and 70% inhibition of the
metabolism by smooth muscle catalase of both endogenously produced
and exogenous (100 [mu]M) H2O2, respectively, as measured by the
H2O2-dependent co-oxidation of methanol to formaldehyde. A similar
treatment of purified catalase with NO caused subsequent inhibition
of its ability to metabolize H2O2, associated with changes in the
spectra of catalase (increases in the absorbance at 535 and 570 nm)
to a species that resembled compound II, an inactive form of
catalase. The exposure of pulmonary arteries to NO also resulted in
the detection of H2O2 release (by catalase-inhibitable
luminol/peroxidase-chemiluminescence). Thus, exposure of pulmonary
arteries to increased physiological levels of NO may promote altered
vasoactive responses involving H2O2 as a result of the inhibition of
catalase.
Received 11 December 1995; accepted in final form 9 April 1996.
APS Manuscript Number H1149-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96