Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets

F. Domoki, James V. Perciaccante, Roland Veltkamp, Greg Robins, F. Bari, Thomas M. Louis, David W. Busija

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have previously shown that cycloheximide (CHX) preserved neuronal function after global cerebral ischemia in piglets, in a manner similar to indomethacin. To elucidate the mechanism of this protection, we tested the hypothesis that CHX would inhibit cyclooxygenase (COX) activity in the piglet cerebral cortex and vasculature. Pial arteriolar responses to hypercapnia, arterial hypotension, and sodium nitroprusside (SNP) were determined before and 20 min after treatment with CHX (0.3-1 mg/kg iv) using a closed cranial window and intravital microscopy. We also determined baseline and arachidonic acid (AA)-stimulated cortical PGF(2α) and 6-keto-PGF(1α) production before and 20-60 rain after CHX (1 mg/kg iv) treatment, using ELISA kits. CHX did not affect baseline diameters (~100 μm) but significantly decreased arteriolar dilation to COX-dependent stimuli, such as hypercapnia and hypotension, but not to COX-independent SNP. In the 1 mg/kg CHX-treated group, increases in vascular diameters were reduced from 22 ± 2 to 10 ± 2%, from 49 ± 5 to 31 ± 3% (means ± SE, 5 and 10% CO2, respectively, n = 8), from 12 ± 3 to 3 ± 1%, and from 26 ± 5 to 6 ± 2% (~25 and 40% decreases in blood pressure, respectively, n = 6). CHX also inhibited conversion of exogenous AA to both PGF(2α) and 6-keto-PGF(1α); for example, 20 min after CHX treatment 10 μg/ml AA-stimulated PGF(2α) concentrations in the artificial cerebrospinal fluid decreased from 14.28 ± 3.04 to 5.90 ± 1.26 ng/ml (n = 9). Thus CHX rapidly decreases COX activity in the piglet cerebral cortex. This result may explain in part the preservation of neuronal function of CHX in cerebral ischemia.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number3 46-3
Publication statusPublished - Sep 1999

Fingerprint

Cycloheximide
Prostaglandin-Endoperoxide Synthases
Dilatation
Prostaglandins F
Arachidonic Acid
Hypercapnia
Nitroprusside
Brain Ischemia
Cerebral Cortex
Hypotension
Rain
Indomethacin
Blood Vessels
Cerebrospinal Fluid
Therapeutics
Enzyme-Linked Immunosorbent Assay
Blood Pressure

Keywords

  • Arachidonic acid
  • Arterial hypotension
  • Cerebral blood flow
  • Hypercapnia
  • Prostaglandin H synthase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets. / Domoki, F.; Perciaccante, James V.; Veltkamp, Roland; Robins, Greg; Bari, F.; Louis, Thomas M.; Busija, David W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 277, No. 3 46-3, 09.1999.

Research output: Contribution to journalArticle

Domoki, F. ; Perciaccante, James V. ; Veltkamp, Roland ; Robins, Greg ; Bari, F. ; Louis, Thomas M. ; Busija, David W. / Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets. In: American Journal of Physiology - Heart and Circulatory Physiology. 1999 ; Vol. 277, No. 3 46-3.
@article{31174c3ebbfe4fd2bd1a1d50908b9dba,
title = "Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets",
abstract = "We have previously shown that cycloheximide (CHX) preserved neuronal function after global cerebral ischemia in piglets, in a manner similar to indomethacin. To elucidate the mechanism of this protection, we tested the hypothesis that CHX would inhibit cyclooxygenase (COX) activity in the piglet cerebral cortex and vasculature. Pial arteriolar responses to hypercapnia, arterial hypotension, and sodium nitroprusside (SNP) were determined before and 20 min after treatment with CHX (0.3-1 mg/kg iv) using a closed cranial window and intravital microscopy. We also determined baseline and arachidonic acid (AA)-stimulated cortical PGF(2α) and 6-keto-PGF(1α) production before and 20-60 rain after CHX (1 mg/kg iv) treatment, using ELISA kits. CHX did not affect baseline diameters (~100 μm) but significantly decreased arteriolar dilation to COX-dependent stimuli, such as hypercapnia and hypotension, but not to COX-independent SNP. In the 1 mg/kg CHX-treated group, increases in vascular diameters were reduced from 22 ± 2 to 10 ± 2{\%}, from 49 ± 5 to 31 ± 3{\%} (means ± SE, 5 and 10{\%} CO2, respectively, n = 8), from 12 ± 3 to 3 ± 1{\%}, and from 26 ± 5 to 6 ± 2{\%} (~25 and 40{\%} decreases in blood pressure, respectively, n = 6). CHX also inhibited conversion of exogenous AA to both PGF(2α) and 6-keto-PGF(1α); for example, 20 min after CHX treatment 10 μg/ml AA-stimulated PGF(2α) concentrations in the artificial cerebrospinal fluid decreased from 14.28 ± 3.04 to 5.90 ± 1.26 ng/ml (n = 9). Thus CHX rapidly decreases COX activity in the piglet cerebral cortex. This result may explain in part the preservation of neuronal function of CHX in cerebral ischemia.",
keywords = "Arachidonic acid, Arterial hypotension, Cerebral blood flow, Hypercapnia, Prostaglandin H synthase",
author = "F. Domoki and Perciaccante, {James V.} and Roland Veltkamp and Greg Robins and F. Bari and Louis, {Thomas M.} and Busija, {David W.}",
year = "1999",
month = "9",
language = "English",
volume = "277",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "3 46-3",

}

TY - JOUR

T1 - Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets

AU - Domoki, F.

AU - Perciaccante, James V.

AU - Veltkamp, Roland

AU - Robins, Greg

AU - Bari, F.

AU - Louis, Thomas M.

AU - Busija, David W.

PY - 1999/9

Y1 - 1999/9

N2 - We have previously shown that cycloheximide (CHX) preserved neuronal function after global cerebral ischemia in piglets, in a manner similar to indomethacin. To elucidate the mechanism of this protection, we tested the hypothesis that CHX would inhibit cyclooxygenase (COX) activity in the piglet cerebral cortex and vasculature. Pial arteriolar responses to hypercapnia, arterial hypotension, and sodium nitroprusside (SNP) were determined before and 20 min after treatment with CHX (0.3-1 mg/kg iv) using a closed cranial window and intravital microscopy. We also determined baseline and arachidonic acid (AA)-stimulated cortical PGF(2α) and 6-keto-PGF(1α) production before and 20-60 rain after CHX (1 mg/kg iv) treatment, using ELISA kits. CHX did not affect baseline diameters (~100 μm) but significantly decreased arteriolar dilation to COX-dependent stimuli, such as hypercapnia and hypotension, but not to COX-independent SNP. In the 1 mg/kg CHX-treated group, increases in vascular diameters were reduced from 22 ± 2 to 10 ± 2%, from 49 ± 5 to 31 ± 3% (means ± SE, 5 and 10% CO2, respectively, n = 8), from 12 ± 3 to 3 ± 1%, and from 26 ± 5 to 6 ± 2% (~25 and 40% decreases in blood pressure, respectively, n = 6). CHX also inhibited conversion of exogenous AA to both PGF(2α) and 6-keto-PGF(1α); for example, 20 min after CHX treatment 10 μg/ml AA-stimulated PGF(2α) concentrations in the artificial cerebrospinal fluid decreased from 14.28 ± 3.04 to 5.90 ± 1.26 ng/ml (n = 9). Thus CHX rapidly decreases COX activity in the piglet cerebral cortex. This result may explain in part the preservation of neuronal function of CHX in cerebral ischemia.

AB - We have previously shown that cycloheximide (CHX) preserved neuronal function after global cerebral ischemia in piglets, in a manner similar to indomethacin. To elucidate the mechanism of this protection, we tested the hypothesis that CHX would inhibit cyclooxygenase (COX) activity in the piglet cerebral cortex and vasculature. Pial arteriolar responses to hypercapnia, arterial hypotension, and sodium nitroprusside (SNP) were determined before and 20 min after treatment with CHX (0.3-1 mg/kg iv) using a closed cranial window and intravital microscopy. We also determined baseline and arachidonic acid (AA)-stimulated cortical PGF(2α) and 6-keto-PGF(1α) production before and 20-60 rain after CHX (1 mg/kg iv) treatment, using ELISA kits. CHX did not affect baseline diameters (~100 μm) but significantly decreased arteriolar dilation to COX-dependent stimuli, such as hypercapnia and hypotension, but not to COX-independent SNP. In the 1 mg/kg CHX-treated group, increases in vascular diameters were reduced from 22 ± 2 to 10 ± 2%, from 49 ± 5 to 31 ± 3% (means ± SE, 5 and 10% CO2, respectively, n = 8), from 12 ± 3 to 3 ± 1%, and from 26 ± 5 to 6 ± 2% (~25 and 40% decreases in blood pressure, respectively, n = 6). CHX also inhibited conversion of exogenous AA to both PGF(2α) and 6-keto-PGF(1α); for example, 20 min after CHX treatment 10 μg/ml AA-stimulated PGF(2α) concentrations in the artificial cerebrospinal fluid decreased from 14.28 ± 3.04 to 5.90 ± 1.26 ng/ml (n = 9). Thus CHX rapidly decreases COX activity in the piglet cerebral cortex. This result may explain in part the preservation of neuronal function of CHX in cerebral ischemia.

KW - Arachidonic acid

KW - Arterial hypotension

KW - Cerebral blood flow

KW - Hypercapnia

KW - Prostaglandin H synthase

UR - http://www.scopus.com/inward/record.url?scp=0032887640&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032887640&partnerID=8YFLogxK

M3 - Article

C2 - 10484435

AN - SCOPUS:0032887640

VL - 277

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 3 46-3

ER -