Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral microvessels

Alie Kanu, David Gilpin, Alexander L. Fedinec, Charles Leffler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Products of arachidonic acid (AA) metabolism by cyclooxygenase (Cox) are important in regulation of neonatal cerebral circulation. The brain and cerebral microvessels also express heme oxygenase (HO) that metabolizes heme to carbon monoxide (CO), biliverdin, and iron. The purpose of this study in newborn pig cerebral microvessels was to address the hypothesis that Cox products affect HO activity and HO products affect Cox activity. AA (2.0-20 μM) increased prostaglandin E2 (PGE2) measured by radioimmunoassay (RIA) and also CO measured by gas chromatography/mass spectrometry (GC/MS). Further, 10-4 M indomethacin, which inhibited Cox, reduced both AA and heme-induced CO production. Conversely, neither exogenous 2 × 10 -6 M heme, which markedly increased CO production, nor the inhibitor of HO, chromium mesoporphyrin, altered PGE2 synthesis. Because AA metabolism by Cox generates both prostanoids and superoxides, we determined the effects of the predominant prostanoid and superoxide on CO production. Although PGE2 caused a small increase in CO production, xanthine oxidase plus hypoxanthine, which produces superoxide, strongly stimulated the production of CO by cerebral microvessels. This increase was mildly attenuated by catalase. These data suggest that Cox-catalyzed AA metabolites, most likely superoxide and/or a subsequent reactive oxygen species, increase cerebrovascular CO production. This increase seems to be caused, at least in part, by the elevation of HO-2 catalytic activity. Conversely, Cox activity is not affected by HO-catalyzed heme metabolites. These data suggest that some cerebrovascular functions attributable to Cox activity could be mediated by CO.

Original languageEnglish (US)
Pages (from-to)181-185
Number of pages5
JournalExperimental Biology and Medicine
Volume231
Issue number2
DOIs
StatePublished - Jan 1 2006

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Carbon Monoxide
Prostaglandin-Endoperoxide Synthases
Microvessels
Heme Oxygenase (Decyclizing)
Heme
Arachidonic Acid
Superoxides
Dinoprostone
Metabolites
Metabolism
Prostaglandins
Cerebrovascular Circulation
Biliverdine
Hypoxanthine
Xanthine Oxidase
Indomethacin
Gas chromatography
Catalase
Gas Chromatography-Mass Spectrometry
Radioimmunoassay

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral microvessels. / Kanu, Alie; Gilpin, David; Fedinec, Alexander L.; Leffler, Charles.

In: Experimental Biology and Medicine, Vol. 231, No. 2, 01.01.2006, p. 181-185.

Research output: Contribution to journalArticle

Kanu, Alie ; Gilpin, David ; Fedinec, Alexander L. ; Leffler, Charles. / Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral microvessels. In: Experimental Biology and Medicine. 2006 ; Vol. 231, No. 2. pp. 181-185.
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