Activation of the Arachidonate 5‐Lipoxygenase Pathway in the Canine Basilar Artery After Experimental Subarachnoidal Hemorrhage

Abstract

Severe cerebral vasospasm as confirmed by an‐giography 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 leu‐kotrienes B₄ (85 ± 12 pmol/mg protein, n = 3) and C₄ (72 ± 14 pmol/mg), in addition to 5(S)‐hydroxy‐6,8,l 1,14‐ei‐cosatetraenoic acid. Structural elucidations of these metabolites were performed by radioimmunoassays or gas chro‐matography‐mass spectrometry, following purification with HPLC. The artery of the untreated dog produced none of these compounds from either exogenous or endogenous ar‐achidonic 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.