AJP - Heart and Circulatory Physiology, Vol 270, Issue 6 2184-H2190, Copyright © 1996 by American Physiological Society
Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries
L. Wiklund, C. G. McGregor and V. M. Miller
Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
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(-4)M) plus xanthine oxidase (0.015 U/ml) for 1
h in the absence and presence of either superoxide dismutase (SOD, 150
U/ml), catalase (1,200 U/ml), deferoxamine (10(-3)M), or a combination of
all three scavengers. Xanthine plus xanthine oxidase caused significantly
greater contractions of rings without compared with those with endothelium.
In rings with endothelium, contractions were reduced by SOD or catalase but
not by deferoxamine. Following 1 h of exposure to xanthine plus xanthine
oxidase, endothelium-dependent relaxations to ADP were reduced but not
those to bradykinin or the calcium ionophore A-23187 (calcimycin).
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 SOD 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.
