Production of 20-HETE and its role in autoregulation of cerebral blood flow

Debebe Gebremedhin, Andrew R. Lange, Timothy F. Lowry, M. Reza Taheri, Eric K. Birks, Antal G. Hudetz, Jayashree Narayanan, J R Falck, Hirotsugu Okamoto, Richard J. Roman, Kasem Nithipatikom, William B. Campbell, David R. Harder

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20- HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase- polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [14C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11- enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF.

Original languageEnglish (US)
Pages (from-to)60-65
Number of pages6
JournalCirculation research
Volume87
Issue number1
DOIs
StatePublished - Jul 7 2000

Keywords

  • Arachidonic acid
  • Cerebral blood flow
  • Cytochrome P- 450
  • HETE
  • Homeostasis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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