8456988

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Experiments were designed to determine the effect of oxygen-derived free radicals in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 (temperature = 37 degrees C; pH = 7.4). A radioimmunoassay technique was used to measure production of prostaglandins and thromboxane B2. Xanthine oxidase (1-9 mU/ml, in the presence of 10(-4) M xanthine) and hydrogen peroxide (10(-6) to 10(-4) M) caused concentration-dependent contractions. The removal of endothelium reversed these contractions into relaxations. Contractions to xanthine oxidase and hydrogen peroxide were inhibited in the presence of superoxide dismutase (150 U/ml), catalase (1,200 U/ml), indomethacin (10(-5) M), and SQ 29548 (10(-6) M) but not in the presence of deferoxamine (10(-4) to 10(-3) M) and dimethyl sulfoxide (10(-4) M). NG-monomethyl-L-arginine (3 x 10(-5) M) augmented the contractions to hydrogen peroxide. Xanthine oxidase stimulated production of 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2. The stimulatory effect was prevented by the removal of endothelial cells. These studies suggest that xanthine oxidase causes endothelium-dependent contractions mediated by: 1) hydrogen peroxide-induced stimulation of the endothelial metabolism of arachidonic acid via the cyclooxygenase pathway, leading to activation of prostaglandin H2-thromboxane A2 receptors, and 2) inactivation of basal production of nitric oxide by superoxide anions.

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H859-64

pubmed-meshheading:8456988-Animals, pubmed-meshheading:8456988-Arginine, pubmed-meshheading:8456988-Basilar Artery, pubmed-meshheading:8456988-Cattle, pubmed-meshheading:8456988-Dogs, pubmed-meshheading:8456988-Endothelium, Vascular, pubmed-meshheading:8456988-Free Radicals, pubmed-meshheading:8456988-Hydrogen Peroxide, pubmed-meshheading:8456988-Indomethacin, pubmed-meshheading:8456988-Meclofenamic Acid, pubmed-meshheading:8456988-Muscle, Smooth, Vascular, pubmed-meshheading:8456988-Muscle Contraction, pubmed-meshheading:8456988-Oxygen, pubmed-meshheading:8456988-Prostaglandins, pubmed-meshheading:8456988-Superoxide Dismutase, pubmed-meshheading:8456988-Thromboxane B2, pubmed-meshheading:8456988-Xanthine, pubmed-meshheading:8456988-Xanthine Oxidase, pubmed-meshheading:8456988-Xanthines, pubmed-meshheading:8456988-omega-N-Methylarginine

Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't