Effects of prolonged exposure to oxygen-derived free radicals in
canine pulmonary arteries.
Wiklund, Lars, Christopher G. A. McGregor, Virginia M. Miller.
Division of Thoracic and Cardiovascular Surgery, Department of
Physiology and Biophysics, Mayo Clinic and Foundation, Rochester,
MN
APStracts 2:0507H, 1995.
Experiments were designed to evaluate endothelium-dependent responses
of pulmonary arteries following prolonged exposure to oxygen-derived
free radicals. Rings of canine pulmonary arteries with and without
endothelium were suspended for measurement of isometric force in
organ chambers and incubated with xanthine (10-4M) plus xanthine
oxidase (0.015 U/ml) for one hour in the absence and presence of
either superoxide dismutase (SOD; 150 U/ml), catalase (1200 U/ml),
desferoxamine (10-3M) or a combination of all three scavengers.
Xanthine plus xanthine oxidase caused significantly greater
contractions of rings without compared to with endothelium. In rings
with endothelium, contractions were reduced by SOD or catalase but
not by desferoxamine. Following one hour exposure to xanthine plus
xanthine oxidase, endothelium-dependent relaxations were reduced to
adenosine diphosphate (ADP) but not to bradykinin or the calcium
ionophore A2318. Relaxations to ADP were not corrected by incubation
with the antioxidants used singly or in combination during the
exposure to xanthine plus xanthine oxidase. These results suggest
that oxygen-derived free radicals generated from exogenously applied
xanthine plus xanthine oxidase cause contractions of canine pulmonary
arteries. In addition, even when contractions of rings with
endothelium were prevented by superoxide dismutase and catalase,
subsequent expression of some but not all endothelium-dependent
relaxations were reduced. Therefore, scavenging of oxygen-derived
free radicals may prevent some but not all of the vascular injury
caused by oxygen-derived free radicals.
Received 15 April 1994; accepted in final form 6 November 1995.
APS Manuscript Number H334-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95