Suppression of cortical functional hyperemia to vibrissal stimulation in the rat by epoxygenase inhibitors

Xinqi Peng, Juan R. Carhuapoma, Anish Bhardwaj, Nabil J. Alkayed, John R. Falck, David R. Harder, Richard J. Traystman, Raymond C. Koehler

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Application of glutamate to glial cell cultures stimulates the formation and release of epoxyeicosatrienoic acids (EETs) from arachidonic acid by cytochome P-450 epoxygenases. Epoxygenase inhibitors reduce the cerebral vasodilator response to glutamate and N-methyl-D-aspartate. We tested the hypothesis that epoxygenase inhibitors reduce the somatosensory cortical blood flow response to whisker activation. In chloralose-anesthetized rats, percent changes in cortical perfusion over whisker barrel cortex were measured by laser-Doppler flowmetry during whisker stimulation. Two pharmacologically distinct inhibitors were superfused subdurally: 1) N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH), an epoxygenase substrate inhibitor; and 2) miconazole, a reversible cytochrome P-450 inhibitor acting on the heme moiety. Superfusion with 5 μmol/l MS-PPOH decreased the hyperemic response to whisker stimulation by 28% (from 25 ± 9 to 18 ± 7%, means ± SD, n = 8). With 20 μmol/l MS-PPOH superfusion, the response was decreased by 69% (from 28 ± 9% to 9 ± 4%, n = 8). Superfusion with 20 μmol/l miconazole decreased the flow response by 67% (from 31 ± 6% to 10 ± 3%, n = 8). Subsequent superfusion with vehicle restored the response to 26 ± 11%. Indomethacin did not prevent MS-PPOH inhibition of the flow response, suggesting that EET-related vasodilation was not dependent solely on cyclooxygenase metabolism of 5,6-EET. Neither MS-PPOH nor miconazole changed baseline flow, reduced the blood flow response to an adenosine A2 agonist, or decreased somatosensory evoked potentials. The marked reduction of the cortical flow response to whisker stimulation with two different types of epoxygenase inhibitors indicates that EETs play an important role in the physiological coupling of blood flow to neural activation.

Original languageEnglish (US)
Pages (from-to)H2029-H2037
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number5 52-5
DOIs
StatePublished - Nov 1 2002

Keywords

  • Arachidonic acid
  • Astrocyte
  • Cerebral blood flow
  • Cytochrome P-450
  • Epoxyeicosatrienoic acids
  • Whisker barrel cortex

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Suppression of cortical functional hyperemia to vibrissal stimulation in the rat by epoxygenase inhibitors'. Together they form a unique fingerprint.

Cite this