Journal of Applied Physiology, Vol 71, Issue 3 821-825, Copyright © 1991 by American Physiological Society
Effect of free radicals on pulmonary vascular response to acetylcholine
X. Chen and C. N. Gillis
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
We describe a model of pulmonary endothelial injury caused by
electrolysis-generated free radicals. Rabbit lungs were perfused in situ
with Krebs solution at 37 degrees C containing 30 microM indomethacin.
Electrolysis of this solution for 2 min, with a constant DC current of 20
mA, caused pulmonary vasoconstriction during the passage of current and
converted subsequent acetylcholine-induced vasodilation to
vasoconstriction. Electrolysis also inhibited endothelial-dependent
vasodilation due to the calcium ionophore A23187 but not that due to sodium
nitroprusside, suggesting that smooth muscle function was unaltered, while
that of the endothelium of the lung is specifically modified by the
stimulus. These effects were prevented by a mixture of superoxide dismutase
and catalase or by sodium salicylate, which removes hydroxyl radicals from
solution after electrolysis. Electrolysis-induced endothelial damage was
less functionally obvious when electrolysis was applied during
recirculation of Krebs solution, perhaps because recirculating perfusion
may trigger release of either free radical scavengers or other protective
substances. This technique offers a simple reproducible model to study free
radical-related damage of endothelium in the intact lung.
