Cytochrome P450 monooxygenase mediates arachidonic acid induced coronary microcirculation dilation in dogs

J. L. Fudge, Neal Lee Weintraub, L. A. Brooks, K. C. Dellsperger

Research output: Contribution to journalArticle

Abstract

We recently showed that cytochrome P450 (P450) contributes importantly to canine coronary microvascular dilatation in vivo. P450 metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs), which our laboratory has shown are potent dilators of coronary microvessels. We, therefore, tested the hypothesis that AA-induced coronary microvascular dilation is mediated in part through a P450 pathway. Adult mongrel dogs (n=22) of either sex were anesthetized. A thoracotomy was performed and coronary arterioles (<100 μm) were observed using stroboscopic epi-illumination during the topical application of AA (1, 5, 10 μM) Coronary microvascular responses were examined in the presence of indomethacin (Indo, 5 mg/kg iv) and Indo plus clotrimazole (CLO, 1.8 μM topically, a cytochrome P450 monooxygenase inhibitor). Results (mean ± SEM, *p<0.05 vs baseline). AA (μM. topically) 1 5 10 Baseline 14 ± 4 35 ± 3 61 ± 5 Indo + CLO 9 ± 3 29 ± 3 48 ± 2* Indo alone did not alter AA-induced dilatation. However, Indo+CLO attenuated AA-induced dilatation, whereas responses to nitroprusside were unaffected. These results suggest that AA induced coronary microvascular dilation is mediated in part by a cytochrome P450 pathway.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Microcirculation
Mixed Function Oxygenases
Arachidonic Acid
Cytochrome P-450 Enzyme System
Dilatation
Dogs
Clotrimazole
Arterioles
Nitroprusside
Thoracotomy
Microvessels
Lighting
Indomethacin
Canidae
Scanning electron microscopy
Acids

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Cytochrome P450 monooxygenase mediates arachidonic acid induced coronary microcirculation dilation in dogs. / Fudge, J. L.; Weintraub, Neal Lee; Brooks, L. A.; Dellsperger, K. C.

In: FASEB Journal, Vol. 11, No. 3, 01.12.1997.

Research output: Contribution to journalArticle

@article{2af9735a1d4a46af89dcde544adfd278,
title = "Cytochrome P450 monooxygenase mediates arachidonic acid induced coronary microcirculation dilation in dogs",
abstract = "We recently showed that cytochrome P450 (P450) contributes importantly to canine coronary microvascular dilatation in vivo. P450 metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs), which our laboratory has shown are potent dilators of coronary microvessels. We, therefore, tested the hypothesis that AA-induced coronary microvascular dilation is mediated in part through a P450 pathway. Adult mongrel dogs (n=22) of either sex were anesthetized. A thoracotomy was performed and coronary arterioles (<100 μm) were observed using stroboscopic epi-illumination during the topical application of AA (1, 5, 10 μM) Coronary microvascular responses were examined in the presence of indomethacin (Indo, 5 mg/kg iv) and Indo plus clotrimazole (CLO, 1.8 μM topically, a cytochrome P450 monooxygenase inhibitor). Results (mean ± SEM, *p<0.05 vs baseline). AA (μM. topically) 1 5 10 Baseline 14 ± 4 35 ± 3 61 ± 5 Indo + CLO 9 ± 3 29 ± 3 48 ± 2* Indo alone did not alter AA-induced dilatation. However, Indo+CLO attenuated AA-induced dilatation, whereas responses to nitroprusside were unaffected. These results suggest that AA induced coronary microvascular dilation is mediated in part by a cytochrome P450 pathway.",
author = "Fudge, {J. L.} and Weintraub, {Neal Lee} and Brooks, {L. A.} and Dellsperger, {K. C.}",
year = "1997",
month = "12",
day = "1",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Cytochrome P450 monooxygenase mediates arachidonic acid induced coronary microcirculation dilation in dogs

AU - Fudge, J. L.

AU - Weintraub, Neal Lee

AU - Brooks, L. A.

AU - Dellsperger, K. C.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - We recently showed that cytochrome P450 (P450) contributes importantly to canine coronary microvascular dilatation in vivo. P450 metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs), which our laboratory has shown are potent dilators of coronary microvessels. We, therefore, tested the hypothesis that AA-induced coronary microvascular dilation is mediated in part through a P450 pathway. Adult mongrel dogs (n=22) of either sex were anesthetized. A thoracotomy was performed and coronary arterioles (<100 μm) were observed using stroboscopic epi-illumination during the topical application of AA (1, 5, 10 μM) Coronary microvascular responses were examined in the presence of indomethacin (Indo, 5 mg/kg iv) and Indo plus clotrimazole (CLO, 1.8 μM topically, a cytochrome P450 monooxygenase inhibitor). Results (mean ± SEM, *p<0.05 vs baseline). AA (μM. topically) 1 5 10 Baseline 14 ± 4 35 ± 3 61 ± 5 Indo + CLO 9 ± 3 29 ± 3 48 ± 2* Indo alone did not alter AA-induced dilatation. However, Indo+CLO attenuated AA-induced dilatation, whereas responses to nitroprusside were unaffected. These results suggest that AA induced coronary microvascular dilation is mediated in part by a cytochrome P450 pathway.

AB - We recently showed that cytochrome P450 (P450) contributes importantly to canine coronary microvascular dilatation in vivo. P450 metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs), which our laboratory has shown are potent dilators of coronary microvessels. We, therefore, tested the hypothesis that AA-induced coronary microvascular dilation is mediated in part through a P450 pathway. Adult mongrel dogs (n=22) of either sex were anesthetized. A thoracotomy was performed and coronary arterioles (<100 μm) were observed using stroboscopic epi-illumination during the topical application of AA (1, 5, 10 μM) Coronary microvascular responses were examined in the presence of indomethacin (Indo, 5 mg/kg iv) and Indo plus clotrimazole (CLO, 1.8 μM topically, a cytochrome P450 monooxygenase inhibitor). Results (mean ± SEM, *p<0.05 vs baseline). AA (μM. topically) 1 5 10 Baseline 14 ± 4 35 ± 3 61 ± 5 Indo + CLO 9 ± 3 29 ± 3 48 ± 2* Indo alone did not alter AA-induced dilatation. However, Indo+CLO attenuated AA-induced dilatation, whereas responses to nitroprusside were unaffected. These results suggest that AA induced coronary microvascular dilation is mediated in part by a cytochrome P450 pathway.

UR - http://www.scopus.com/inward/record.url?scp=33750146729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750146729&partnerID=8YFLogxK

M3 - Article

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -