Activation of the arachidonate 5-lipoxygenase pathway in the canine basilar artery after experimental subarachnoidal hemorrhage.
Severe cerebral vasospasm as confirmed by angiography was induced in dogs by injection of autologous blood into the cisterna magna, and the resultant leukotriene formation in the isolated basilar artery was examined. When stimulated with calcium ionophore (A 23187), the arteries of the treated animals produced a significant amount of leukotrienes B4 (85 +/- 12 pmol/mg protein, n = 3) and C4 (72 +/- 14 pmol/mg), in addition to 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid. Structural elucidations of these metabolites were performed by radioimmunoassays or gas chromatography-mass spectrometry, following purification with HPLC. The artery of the untreated dog produced none of these compounds from either exogenous or endogenous arachidonic acid, under stimulation with the calcium ionophore. However, the homogenates from both animals converted exogenous leukotriene A4 to leukotrienes B4 and C4. These observations suggest that the normal basilar artery contains no detectable amount of 5-lipoxygenase, and that a prominent activation of this enzyme occurred (2.1 nmol 5-HETE/5 min/mg of protein) after subarachnoidal hemorrhage. The observation that fatty acid hydroperoxides stimulated the 5-lipoxygenase activity indicates a possible role of lipid peroxides in the development of vasospasm.
Shimizu
T
T
Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo, Japan.
Watanabe
T
T
Asano
T
T
Seyama
Y
Y
Takakura
K
K
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001488:Basilar Artery / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000494:pharmacology; D011863:Radioimmunoassay; D013189:SRS-A / Q000096:biosynthesis; D013345:Subarachnoid Hemorrhage / Q000201:enzymology*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase