Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow. Am J Physiol 1996 Oct;271(4 Pt 2):H1541-6
Date
10/01/1996Pubmed ID
8897950DOI
10.1152/ajpheart.1996.271.4.H1541Scopus ID
2-s2.0-33750807720 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
Arachidonic acid (AA) is metabolized by the cytochrome P-450 (P-450) epoxygenase pathway to epoxyeicosatrienoic acids (EETs) in the brain parenchymal tissue and perivascular astrocytes. EETs dilate cerebral microvessels and enhance K+ current in cerebrovascular smooth muscle cells. In the current study, the effect of a subdural administration of miconazole, an inhibitor of P-450 epoxygenase, on microvascular perfusion of rat cerebral cortex was evaluated using laser-Doppler flowmetry (LDF) Baseline cerebral blood flow (CBF) decreased by 29.7 +/- 7.3% (n = 5) after administration of 20 microM miconazole into the subdural space for 30 min. Responses of CBF to sodium nitroprusside and 5-hydroxytryptamine were unaltered by miconazole treatment. Administration of vehicle alone in time-control experiments had no effect on CBF. In other experiments, the effects of miconazole on the metabolism of [14C]AA by cultured rat astrocytes and on nitric oxide synthase activity in homogenates of rat brain were examined. Miconazole inhibited conversion of AA to EETs by cultured astrocytes but had no effect on the conversion of L-arginine to L-citrulline by homogenates of rat brain. These results implicate endogenous P-450 epoxides of AA in the regulation of basal blood flow in cerebral microcirculation.
Author List
Alkayed NJ, Birks EK, Hudetz AG, Roman RJ, Henderson L, Harder DRMESH terms used to index this publication - Major topics in bold
AnimalsArachidonic Acid
Astrocytes
Brain
Cells, Cultured
Cerebrovascular Circulation
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Male
Miconazole
Microcirculation
Nitric Oxide Synthase
Oxygenases
Rats
Rats, Sprague-Dawley
