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 journalArticle

258 Citations (Scopus)

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
StatePublished - Jul 7 2000

Fingerprint

Cerebrovascular Circulation
Homeostasis
Pressure
Arachidonic Acid
Constriction
Muscles
Cerebral Arteries
Middle Cerebral Artery
Vasoconstrictor Agents
Microsomes
Microvessels
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Vasoconstriction
Reverse Transcriptase Polymerase Chain Reaction
Gas Chromatography-Mass Spectrometry
Cytochrome P-450 Enzyme System
In Situ Hybridization
Blood Vessels
Arterial Pressure
Protein Isoforms

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Gebremedhin, D., Lange, A. R., Lowry, T. F., Taheri, M. R., Birks, E. K., Hudetz, A. G., ... Harder, D. R. (2000). Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circulation Research, 87(1), 60-65.

Production of 20-HETE and its role in autoregulation of cerebral blood flow. / Gebremedhin, Debebe; Lange, Andrew R.; Lowry, Timothy F.; Taheri, M. Reza; Birks, Eric K.; Hudetz, Antal G.; Narayanan, Jayashree; Falck, J R; Okamoto, Hirotsugu; Roman, Richard J.; Nithipatikom, Kasem; Campbell, William B.; Harder, David R.

In: Circulation Research, Vol. 87, No. 1, 07.07.2000, p. 60-65.

Research output: Contribution to journalArticle

Gebremedhin, D, Lange, AR, Lowry, TF, Taheri, MR, Birks, EK, Hudetz, AG, Narayanan, J, Falck, JR, Okamoto, H, Roman, RJ, Nithipatikom, K, Campbell, WB & Harder, DR 2000, 'Production of 20-HETE and its role in autoregulation of cerebral blood flow', Circulation Research, vol. 87, no. 1, pp. 60-65.
Gebremedhin D, Lange AR, Lowry TF, Taheri MR, Birks EK, Hudetz AG et al. Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circulation Research. 2000 Jul 7;87(1):60-65.
Gebremedhin, Debebe ; Lange, Andrew R. ; Lowry, Timothy F. ; Taheri, M. Reza ; Birks, Eric K. ; Hudetz, Antal G. ; Narayanan, Jayashree ; Falck, J R ; Okamoto, Hirotsugu ; Roman, Richard J. ; Nithipatikom, Kasem ; Campbell, William B. ; Harder, David R. / Production of 20-HETE and its role in autoregulation of cerebral blood flow. In: Circulation Research. 2000 ; Vol. 87, No. 1. pp. 60-65.
@article{3bff80de20754ee287c92a0f1ce50c20,
title = "Production of 20-HETE and its role in autoregulation of cerebral blood flow",
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.",
keywords = "Arachidonic acid, Cerebral blood flow, Cytochrome P- 450, HETE, Homeostasis",
author = "Debebe Gebremedhin and Lange, {Andrew R.} and Lowry, {Timothy F.} and Taheri, {M. Reza} and Birks, {Eric K.} and Hudetz, {Antal G.} and Jayashree Narayanan and Falck, {J R} and Hirotsugu Okamoto and Roman, {Richard J.} and Kasem Nithipatikom and Campbell, {William B.} and Harder, {David R.}",
year = "2000",
month = "7",
day = "7",
language = "English (US)",
volume = "87",
pages = "60--65",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Production of 20-HETE and its role in autoregulation of cerebral blood flow

AU - Gebremedhin, Debebe

AU - Lange, Andrew R.

AU - Lowry, Timothy F.

AU - Taheri, M. Reza

AU - Birks, Eric K.

AU - Hudetz, Antal G.

AU - Narayanan, Jayashree

AU - Falck, J R

AU - Okamoto, Hirotsugu

AU - Roman, Richard J.

AU - Nithipatikom, Kasem

AU - Campbell, William B.

AU - Harder, David R.

PY - 2000/7/7

Y1 - 2000/7/7

N2 - 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.

AB - 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.

KW - Arachidonic acid

KW - Cerebral blood flow

KW - Cytochrome P- 450

KW - HETE

KW - Homeostasis

UR - http://www.scopus.com/inward/record.url?scp=0034617142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034617142&partnerID=8YFLogxK

M3 - Article

VL - 87

SP - 60

EP - 65

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -