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Brain Synthesis and Cerebrovascular Action of Epoxygenase Metabolites of Arachidonic Acid
Author(s) -
Amruthesh Shivachar C.,
Falck J. R.,
Ellis Earl F.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09749.x
Subject(s) - epoxygenase , arachidonic acid , action (physics) , chemistry , medicine , pharmacology , neuroscience , endocrinology , biology , biochemistry , enzyme , physics , quantum mechanics
The purpose of this study was to determine if whole brain makes epoxygenase metabolites of arachidonic acid and, if so, whether they are vasoactive on the cerebral microcirculation. Blood‐free mouse brain slices were incubated with exogenous radiolabeled arachidonic acid, and the extracted metabolites were resolved by HPLC. Metabolite structures were confirmed by gas chromatography/mass spectrometry. In addition to prostaglandins, leukotriene B 4 , and hydroxyeicosatetraenoic acids, mouse brain metabolized arachidonic acid into several other compounds. Among them, we identified 5,6‐ and 14,15‐epoxyeicosatrienoic acid. Next, we tested the effect of topical application of brain‐synthesized 5,6‐epoxyeicosatrienoic acid and synthetic epoxyeicosatrienoic acids on in vivo rabbit cerebral arteriolar diameter using the cranial window technique and in vivo microscopy. Brain‐synthesized 5,6‐epoxyeicosatrienoic acid caused a transient 28% arteriolar dilation, similar to that produced by 5 μg/ml of synthetic 5,6‐epoxyeicosatrienoic acid. A concentration of synthetic 14,15‐ and 11,12‐epoxyeicosatrienoic acid of 5 μg/ml CSF had little or no effect on diameter, whereas 8,9‐epoxyeicosatrienoic acid caused a maximum dilation of 8%. These studies suggest that brain‐synthesized 5,6‐epoxyeicosatrienoic acid may play a role in the normal or pathophysiological regulation of the cerebral microcirculation.