Cerebral arteries can generate 5- and 15-hydroxyeicosatetraenoic acid from arachidonic acid.
Products of the lipoxygenase pathway have been implicated in the development of the cerebrovascular spasm that arises after subarachnoid hemorrhage. In particular the hydroperoxyeicosatetranenoic acids (HPETEs), which are unstable and break down rapidly to the corresponding 5-hydroxy acids (HETEs), are vasoconstrictor agents that mimic some aspects of cerebrovascular spasm. It is not, however, well established whether segments of cerebral artery can manufacture these products. We have studied the lipoxygenase product profile of cerebral arteries stimulated with arachidonic acid. Rings of bovine cerebral arteries were incubated in Krebs solution containing arachidonic acid. The lipoxygenase products were studied using high performance liquid chromatography. The largest peaks had the retention times of 5- and 15-HETEs, and the identity of these peaks was confirmed using specific radioimmunoassays. Stimulation with arachidonic acid resulted in a time- and dose-dependent increase in the formation of both HETEs, with 15-HETE being most abundant. The release of both HETEs was markedly reduced in the presence of AA-861, an inhibitor of lipoxygenase, but not with the cyclooxygenase inhibitor indomethacin. These data are thus consistent with our previous suggestion that the contractile activity of arachidonic acid in cerebral arteries arises, at least in part, from HPETE formation and with a possible role for these compounds in cerebral vasospasm.
Schulz
R
R
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Jancar
S
S
Cook
D A
DA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D016227:Benzoquinones; D002417:Cattle; D002536:Cerebral Arteries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011863:Radioimmunoassay
D001095:Arachidonic Acids; D016227:Benzoquinones; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D007213:Indomethacin