Dual regulation of the cerebral microvasculature by epoxyeicosatrienoic acids

Epoxyeicosatrienoic acids (EETs) are lipid metabolites that are synthesized in vascular endothelial cells. They are released by stimulation of their muscarinic receptors, and induce vaso-relaxation of cerebral blood vessels. In addition, cytochrome P450 epoxygenase enzymes, which catalyze the formation of epoxyeicosatrienoic acids, especially after stimulation by the excitatory neurotransmitter glutamate, are present in astrocytes, an abundant cell type in the brain that extends foot processes onto the cerebral microvessels. Using a modification of an efficient, recently developed, fluorescent assay, we have detected the presence of EETs in endothelial cells cultured from the cortex of rat brains as well as in neonatal astrocytes. We propose that both these cell types provide a dual supply of EETs to increase cerebral blood flow in order to meet systemic as well as localized nutrient demands of cells in the brain.