Effect of free radicals on pulmonary vascular response to acetylcholine.
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.
Chen
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Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Gillis
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D012980:Sodium Salicylate / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D005609:Free Radicals; D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D000001:Calcimycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001285:Atropine; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D000109:Acetylcholine; D012980:Sodium Salicylate