Activation of cardiac afferents by arachidonic acid

Relative contributions of the different metabolic pathways

S. Y. Sun, W. Wang, Harold D Schultz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and cytochrome P450 (P450) to produce a variety of bioactive products. The role of AA and its metabolites in the activation of cardiac afferents have not been investigated. This study aimed to examine the effects of exogenous AA on the activity of cardiac afferents and to evaluate the relative contributions of its three metabolic pathways in these effects. Single-unit activity of cardiac chemosensitive afferents was recorded from the cervical vagi in anesthetized rats, and their response to epicardial application of AA was measured with and without blockade of COX, 5-LOX and P450 respectively. The effects of some AA metabolites from the different pathways on the activity of cardiac afferents were also examined. AA (0.3-30 nmol) activated cardiac vagal afferents dose-dependently. Blockade of either COX (indomethacin, 5 mg/kg, iv) or P450 (17-octadecynoicacid, 1 mg/kg, iv), but not of 5-LOX (nordihydroguaiaretic acid, 5 mg/kg, iv), attenuated AA-induced activation of the cardiac afferents. Simultaneous blockade of COX and P450 totally blocked the activation evoked by AA. Among the tested metabolites from COX, PGE2, PGIZ and TXA2 activated cardiac afferents, while TXB2 and PGF, did not. 20-HETE and 14, 15-EET, the metabolites from P450 which were tested, also activated cardiac afferents. These data suggest that the AA-induced activation of cardiac vagal afferents is mediated by the metabolites from COX and P450, but not 5-LOX pathways in normal rats.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Metabolic Networks and Pathways
arachidonic acid
Arachidonic Acid
biochemical pathways
Chemical activation
prostaglandin synthase
Prostaglandin-Endoperoxide Synthases
Metabolites
Arachidonate 5-Lipoxygenase
lipoxygenase
metabolites
Rats
nordihydroguaiaretic acid
Masoprocol
Dinoprost
indomethacin
rats
Dinoprostone
cytochrome P-450
Indomethacin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Activation of cardiac afferents by arachidonic acid : Relative contributions of the different metabolic pathways. / Sun, S. Y.; Wang, W.; Schultz, Harold D.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

@article{e3549c7ed7df473897c28c127f560aca,
title = "Activation of cardiac afferents by arachidonic acid: Relative contributions of the different metabolic pathways",
abstract = "Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and cytochrome P450 (P450) to produce a variety of bioactive products. The role of AA and its metabolites in the activation of cardiac afferents have not been investigated. This study aimed to examine the effects of exogenous AA on the activity of cardiac afferents and to evaluate the relative contributions of its three metabolic pathways in these effects. Single-unit activity of cardiac chemosensitive afferents was recorded from the cervical vagi in anesthetized rats, and their response to epicardial application of AA was measured with and without blockade of COX, 5-LOX and P450 respectively. The effects of some AA metabolites from the different pathways on the activity of cardiac afferents were also examined. AA (0.3-30 nmol) activated cardiac vagal afferents dose-dependently. Blockade of either COX (indomethacin, 5 mg/kg, iv) or P450 (17-octadecynoicacid, 1 mg/kg, iv), but not of 5-LOX (nordihydroguaiaretic acid, 5 mg/kg, iv), attenuated AA-induced activation of the cardiac afferents. Simultaneous blockade of COX and P450 totally blocked the activation evoked by AA. Among the tested metabolites from COX, PGE2, PGIZ and TXA2 activated cardiac afferents, while TXB2 and PGF2α, did not. 20-HETE and 14, 15-EET, the metabolites from P450 which were tested, also activated cardiac afferents. These data suggest that the AA-induced activation of cardiac vagal afferents is mediated by the metabolites from COX and P450, but not 5-LOX pathways in normal rats.",
author = "Sun, {S. Y.} and W. Wang and Schultz, {Harold D}",
year = "1998",
month = "3",
day = "20",
language = "English (US)",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Activation of cardiac afferents by arachidonic acid

T2 - Relative contributions of the different metabolic pathways

AU - Sun, S. Y.

AU - Wang, W.

AU - Schultz, Harold D

PY - 1998/3/20

Y1 - 1998/3/20

N2 - Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and cytochrome P450 (P450) to produce a variety of bioactive products. The role of AA and its metabolites in the activation of cardiac afferents have not been investigated. This study aimed to examine the effects of exogenous AA on the activity of cardiac afferents and to evaluate the relative contributions of its three metabolic pathways in these effects. Single-unit activity of cardiac chemosensitive afferents was recorded from the cervical vagi in anesthetized rats, and their response to epicardial application of AA was measured with and without blockade of COX, 5-LOX and P450 respectively. The effects of some AA metabolites from the different pathways on the activity of cardiac afferents were also examined. AA (0.3-30 nmol) activated cardiac vagal afferents dose-dependently. Blockade of either COX (indomethacin, 5 mg/kg, iv) or P450 (17-octadecynoicacid, 1 mg/kg, iv), but not of 5-LOX (nordihydroguaiaretic acid, 5 mg/kg, iv), attenuated AA-induced activation of the cardiac afferents. Simultaneous blockade of COX and P450 totally blocked the activation evoked by AA. Among the tested metabolites from COX, PGE2, PGIZ and TXA2 activated cardiac afferents, while TXB2 and PGF2α, did not. 20-HETE and 14, 15-EET, the metabolites from P450 which were tested, also activated cardiac afferents. These data suggest that the AA-induced activation of cardiac vagal afferents is mediated by the metabolites from COX and P450, but not 5-LOX pathways in normal rats.

AB - Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and cytochrome P450 (P450) to produce a variety of bioactive products. The role of AA and its metabolites in the activation of cardiac afferents have not been investigated. This study aimed to examine the effects of exogenous AA on the activity of cardiac afferents and to evaluate the relative contributions of its three metabolic pathways in these effects. Single-unit activity of cardiac chemosensitive afferents was recorded from the cervical vagi in anesthetized rats, and their response to epicardial application of AA was measured with and without blockade of COX, 5-LOX and P450 respectively. The effects of some AA metabolites from the different pathways on the activity of cardiac afferents were also examined. AA (0.3-30 nmol) activated cardiac vagal afferents dose-dependently. Blockade of either COX (indomethacin, 5 mg/kg, iv) or P450 (17-octadecynoicacid, 1 mg/kg, iv), but not of 5-LOX (nordihydroguaiaretic acid, 5 mg/kg, iv), attenuated AA-induced activation of the cardiac afferents. Simultaneous blockade of COX and P450 totally blocked the activation evoked by AA. Among the tested metabolites from COX, PGE2, PGIZ and TXA2 activated cardiac afferents, while TXB2 and PGF2α, did not. 20-HETE and 14, 15-EET, the metabolites from P450 which were tested, also activated cardiac afferents. These data suggest that the AA-induced activation of cardiac vagal afferents is mediated by the metabolites from COX and P450, but not 5-LOX pathways in normal rats.

UR - http://www.scopus.com/inward/record.url?scp=4243204821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4243204821&partnerID=8YFLogxK

M3 - Article

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -