Role of carbon monoxide in glutamate receptor-induced dilation of newborn pig pial arterioles

James S. Robinson, Alexander L. Fedinec, Charles W. Leffler

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The hypothesis that glutamate dilates pial arterioles of new- born pigs through the production of carbon monoxide (CO) was addressed. Anesthesized newborn pigs were equipped with cranial windows to measure pial arteriolar responses to stimuli. Heme oxygenase (HO) inhibitors added topically inhibited dilation to glutamate and to specific glutamate receptor agonists. The initial dilation to glutamate (10-5 M) was 22% from baseline without an inhibitor and decreased to 9% with the HO inhibitor chromium mesoporphyrin (CrMP). Inhibition of dilation upon HO inhibition was similar when specific glutamate receptor agonists were employed. RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused 24% dilation from the baseline without an inhibitor, and the dilation was decreased to 1% with tin protoporphyrin (SnPP). (RS)-2-amino-3-(3-hydroxy-5-t-butylisoxazol-4-yl)propionic acid (kainate receptors) caused dilation of 18% from baseline without an inhibitor, but only 2% when tin mesoporphyrin was applied. 1-Aminocyclopropanecarboxylic acid (N-methyl-D-aspartate receptors) dilated pial arterioles 33% from baseline in control, but only to 2% in the presence of SnPP. Neither copper mesoporphyrin, which does not inhibit HO, nor light-inactivated CrMP affected the dilations. Furthermore, cerebral microvessels removed from the brain produced CO (stable isotope dilution gas chromatography-mass spectrometry), and this production was dose dependently increased by glutamate and inhibited by metal porphyrin HO inhibitors. These data suggest that dilation of newborn pig pial arterioles to glutamate and specific glutamate receptor agonists involves vascular production of CO. Additional cerebral sources of CO also could be stimulated by glutamate and contribute to the dilation.

Original languageEnglish (US)
Pages (from-to)H2371-H2376
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number6 51-6
StatePublished - Jul 2 2002

Fingerprint

Glutamate Receptors
Arterioles
Carbon Monoxide
Dilatation
Swine
Heme Oxygenase (Decyclizing)
Glutamic Acid
Excitatory Amino Acid Agonists
Kainic Acid Receptors
Porphyrins
Microvessels
N-Methyl-D-Aspartate Receptors
Isotopes
Gas Chromatography-Mass Spectrometry
Blood Vessels
Copper
Metals
Light
Acids
Brain

All Science Journal Classification (ASJC) codes

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

Cite this

Role of carbon monoxide in glutamate receptor-induced dilation of newborn pig pial arterioles. / Robinson, James S.; Fedinec, Alexander L.; Leffler, Charles W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 282, No. 6 51-6, 02.07.2002, p. H2371-H2376.

Research output: Contribution to journalArticle

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