Nitric oxide increases carbon monoxide production by piglet cerebral microvessels

Charles Leffler, Liliya Balabanova, Alexander L. Fedinec, Elena Parfenova

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Carbon monoxide (CO) and nitric oxide (NO) can be involved in the regulation of cerebral circulation. Inhibition of production of either one of these gaseous intercellular messengers inhibits newborn pig cerebral arteriolar dilation to the excitatory amino acid glutamate. Glutamate can increase NO production. Therefore, the present study tests the hypothesis that NO, which is increased by glutamate, stimulates the production of CO by cerebral microvessels. Experiments used freshly isolated cerebral microvessels from piglets that express only heme oxygenase-2 (HO-2). CO production was measured by gas chromatography-mass spectrometry. Although inhibition of nitric oxide synthase (NOS) with Nω-nitro-L-arginine (L-NNA) did not alter basal HO-2 catalytic activity or CO production, L-NNA blocked glutamate stimulation of HO-2 activity and CO production. Furthermore, the NO donor sodium nitroprusside mimicked the actions of glutamate on HO-2 and CO production. The action of NO appears to be via cGMP because 8-bromo-cGMP mimics and 1H-[1,2,4]oxadiazole-[4, 3-a]quinoxalin-1-one (ODQ) blocks glutamate stimulation of CO production and HO-2 catalytic activity. Inhibitors of neither casein kinase nor phosphotidylinositol 3-kinase altered HO-2 catalytic activity. Conversely, inhibition of calmodulin with calmidazolium chloride blocked glutamate stimulation of CO production and reduced HO-2 catalytic activity. These data suggest that glutamate may activate NOS producing NO that leads to CO synthesis via a cGMP-dependent elevation of HO-2 catalytic activity. These results are consistent with the findings in vivo that either HO or NOS inhibition blocks cerebrovascular dilation to glutamate in piglets. ©

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number4 58-4
DOIs
StatePublished - Oct 1 2005

Fingerprint

Carbon Monoxide
Microvessels
Glutamic Acid
Nitric Oxide
Nitric Oxide Synthase
calmidazolium
Dilatation
Cerebrovascular Circulation
Casein Kinases
Oxadiazoles
Quinoxalines
Excitatory Amino Acids
Nitric Oxide Donors
heme oxygenase-2
Nitroprusside
Calmodulin
Gas Chromatography-Mass Spectrometry
Arginine
Phosphotransferases
Swine

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Nitric oxide increases carbon monoxide production by piglet cerebral microvessels. / Leffler, Charles; Balabanova, Liliya; Fedinec, Alexander L.; Parfenova, Elena.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 4 58-4, 01.10.2005.

Research output: Contribution to journalArticle

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AB - Carbon monoxide (CO) and nitric oxide (NO) can be involved in the regulation of cerebral circulation. Inhibition of production of either one of these gaseous intercellular messengers inhibits newborn pig cerebral arteriolar dilation to the excitatory amino acid glutamate. Glutamate can increase NO production. Therefore, the present study tests the hypothesis that NO, which is increased by glutamate, stimulates the production of CO by cerebral microvessels. Experiments used freshly isolated cerebral microvessels from piglets that express only heme oxygenase-2 (HO-2). CO production was measured by gas chromatography-mass spectrometry. Although inhibition of nitric oxide synthase (NOS) with Nω-nitro-L-arginine (L-NNA) did not alter basal HO-2 catalytic activity or CO production, L-NNA blocked glutamate stimulation of HO-2 activity and CO production. Furthermore, the NO donor sodium nitroprusside mimicked the actions of glutamate on HO-2 and CO production. The action of NO appears to be via cGMP because 8-bromo-cGMP mimics and 1H-[1,2,4]oxadiazole-[4, 3-a]quinoxalin-1-one (ODQ) blocks glutamate stimulation of CO production and HO-2 catalytic activity. Inhibitors of neither casein kinase nor phosphotidylinositol 3-kinase altered HO-2 catalytic activity. Conversely, inhibition of calmodulin with calmidazolium chloride blocked glutamate stimulation of CO production and reduced HO-2 catalytic activity. These data suggest that glutamate may activate NOS producing NO that leads to CO synthesis via a cGMP-dependent elevation of HO-2 catalytic activity. These results are consistent with the findings in vivo that either HO or NOS inhibition blocks cerebrovascular dilation to glutamate in piglets. ©

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