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Brain Microvessels Produce 12‐Hydroxyeicosatetraenoic Acid
Author(s) -
Moore Steven A.,
Figard Paul H.,
Spector Arthur A.,
Hart Michael N.
Publication year - 1989
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.1471-4159.1989.tb07345.x
Subject(s) - hydroxyeicosatetraenoic acid , chemistry , biophysics , neuroscience , biochemistry , biology , arachidonic acid , enzyme
Cerebral microvessels isolated from perfused, adult murine brain produce a compound with the chromatographic properties of a monohydroxyeicosatetraenoic acid when incubated with arachidonic acid or stimulated with calcium ionophore A23187. The formation of this arachidonic acid metabolite is not reduced in the presence of the cyclooxy‐genase inhibitor ibuprofen, but it is abolished by the lipoxygenase inhibitor nordihydroguaiaretic acid. Analysis by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonre‐duced derivatives of the metabolite indicate that the compound is 12‐hydroxyeicosatetraenoic acid. Fractions of isolated microvessels enriched with capillaries produce 2.1 times more 12‐hydroxyeicosatetraenoic acid per microgram of protein than do fractions of microvessels enriched with arterioles. These studies confirm that brain microvessels can produce 12‐hydroxyeicosatetraenoic acid and strongly suggest that cerebral endothelia are the primary source of microvessel‐derived 12‐hydroxyeicosatetraenoic acid. They further suggest that in brain injury, the liberation and accumulation of arachidonic acid in cerebral tissues may lead to the production of 12‐hydroxyeicosatetraenoic acid within microvessels. The 12‐hydroxyeicosatetraenoic acid formed in this way may mediate some of the blood‐brain barrier and cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures.