Xanthine oxidase and endothelium dependent relaxation.
Superoxide anion (O2-) generated from xanthine oxidase/xanthine has been used to decrease the half life of endothelium derived relaxing factor (EDRF). However, by itself, xanthine oxidase causes endothelium dependent relaxation. This relaxation is unrelated to the oxidative property of the enzyme since it is not inhibited by allopurinol. In addition, the relaxation is not inhibited by the cyclooxygenase inhibitor, indomethacin, or the phospholipase A2 inhibitor, p-bromophenacyl bromide. On the other hand the relaxation is inhibited by the trypsin inhibitor (TI) from chicken egg white. A similar endothelium dependent relaxation elicited by pancreatin and trypsin is also inhibited by TI. Pancreatin used in the preparation of xanthine oxidase contains trypsin, chymotrypsin and carboxypeptidase. When compared to trypsin both chymotrypsin and carboxypeptidase elicit little relaxation. Thus the endothelium dependent relaxation elicited by xanthine oxidase is likely due to contamination with trypsin. Our results emphasize that when the superoxide generating system, xanthine oxidase/xanthine is used to study the effect of oxygen radicals on EDRF, it is advantageous to ensure that only purified preparations of xanthine oxidase are used.
Thomas
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Ramwell
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D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D004727:Endothelium / Q000502:physiology*; D005189:False Positive Reactions; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010194:Pancreatin / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology*
D013481:Superoxides; D010194:Pancreatin; D014969:Xanthine Oxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D014357:Trypsin