Oxygen-elicited responses in calf coronary arteries: role of h2o2
production via nadh-derived superoxide.
Mohazzab-H., Kamal M., Pawel M. Kaminski, Raisa P. Fayngersh, and
Michael S. Wolin.
Department of Physiology, New York Medical College, Valhalla, NY
10595
APStracts 2:0386H, 1995.
Our previous studies in isolated endothelium-removed calf pulmonary
arteries suggest that PO2-elicited responses are primarily mediated
through modulation of cGMP via changes in the generation of H2O2
originating from superoxide anion (O2.-) produced by NADH oxidase
activity. In the present study, we examined the importance of this
mechanism in PO2-elicited responses of endothelium-removed calf
coronary arteries. NADH oxidase activity was found to be the major
source of O2.- in the homogenate of endothelium-removed calf coronary
arteries detected by lucigenin-elicited chemiluminescence.
Precontracted endothelium-removed calf coronary arteries show a
relaxation to hypoxia, and reoxygenation causes a transient
additional relaxation prior to the recovery of normoxic levels of
force. Under these conditions the detection of O2.- was decreased by
hypoxia and a transient overproduction was observed during
reoxygenation. The relaxation to reoxygenation, but not to hypoxia,
was significantly inhibited by a scavenger of O2.- which prevents the
formation of H2O2 (nitroblue tetrazolium), an inhibitor of NAD(P)H
oxidases and other O2.- generating flavoproteins (diphenyliodonium)
and by inhibition of the stimulation of soluble guanylate cyclase
(LY83583). A scavenger of O2.- that promotes H2O2 formation (Tiron)
did not inhibit the PO2-elicited responses examined. Hypoxia and
diphenyliodonium (but not Tiron) produced decreases in the metabolism
of endogenous H2O2 by catalase (as measured by the H2O2-dependent co
-oxidation of methanol to formaldehyde by catalase), and reoxygenation
caused a stimulation of H2O2 metabolism by catalase. The presence of
endothelium resulted in minor modifications of the PO2 responses
studied, which were partially mediated via prostaglandins and nitric
oxide based on the effects of indomethacin and nitro-L-arginine,
respectively. These results suggest that in calf coronary arteries
the stimulation of guanylate cyclase via H2O2 originating from NADH
-derived O2.- production contributes to the transient relaxation to
post-hypoxic reoxygenation, but not the response to hypoxia.
Received 6 January 1995; accepted in final form 23 August 1995.
APS Manuscript Number H11-5.
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.