Arachidonic acid- and prostaglandin E 2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets

Alie Kanu, Charles Leffler

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Arachidonic acid (AA) and prostaglandin (PG) E 2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10 -8-10 -6 M), PGE2 (10 -8-10 -6 M), iloprost (10 -8-10 -6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE 2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE 2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE 2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 - 10 -5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 - 10 -5 M) and the H 2O 2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE 2. Heme-L-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE 2-induced cerebral vascular dilation is mediated by CO, independent of ROS.

Original languageEnglish (US)
Pages (from-to)2482-2487
Number of pages6
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number6
DOIs
StatePublished - Dec 1 2011

Fingerprint

Carbon Monoxide
Prostaglandins E
Arachidonic Acid
Vasodilation
Reactive Oxygen Species
Iloprost
Dilatation
Catalase
Blood Vessels
Swine
Heme Oxygenase (Decyclizing)
Xanthine Oxidase
Epoprostenol
Prostaglandin-Endoperoxide Synthases
Vasodilator Agents
Indomethacin
Cerebrospinal Fluid

All Science Journal Classification (ASJC) codes

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

Cite this

@article{174008c4f68648b19985d62fb2cee873,
title = "Arachidonic acid- and prostaglandin E 2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets",
abstract = "Arachidonic acid (AA) and prostaglandin (PG) E 2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10 -8-10 -6 M), PGE2 (10 -8-10 -6 M), iloprost (10 -8-10 -6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE 2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE 2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE 2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 - 10 -5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 - 10 -5 M) and the H 2O 2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE 2. Heme-L-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE 2-induced cerebral vascular dilation is mediated by CO, independent of ROS.",
author = "Alie Kanu and Charles Leffler",
year = "2011",
month = "12",
day = "1",
doi = "10.1152/ajpheart.00628.2011",
language = "English (US)",
volume = "301",
pages = "2482--2487",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Arachidonic acid- and prostaglandin E 2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets

AU - Kanu, Alie

AU - Leffler, Charles

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Arachidonic acid (AA) and prostaglandin (PG) E 2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10 -8-10 -6 M), PGE2 (10 -8-10 -6 M), iloprost (10 -8-10 -6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE 2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE 2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE 2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 - 10 -5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 - 10 -5 M) and the H 2O 2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE 2. Heme-L-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE 2-induced cerebral vascular dilation is mediated by CO, independent of ROS.

AB - Arachidonic acid (AA) and prostaglandin (PG) E 2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10 -8-10 -6 M), PGE2 (10 -8-10 -6 M), iloprost (10 -8-10 -6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE 2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE 2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE 2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 - 10 -5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 - 10 -5 M) and the H 2O 2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE 2. Heme-L-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE 2-induced cerebral vascular dilation is mediated by CO, independent of ROS.

UR - http://www.scopus.com/inward/record.url?scp=82855169270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82855169270&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00628.2011

DO - 10.1152/ajpheart.00628.2011

M3 - Article

VL - 301

SP - 2482

EP - 2487

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 6

ER -