Carbon monoxide from heme oxygenase-2 is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation

Mami Ishikawa, Mayumi Kajimura, Takeshi Adachi, Kayo Maruyama, Nobuya Makino, Nobuhito Goda, Tokio Yamaguchi, Eiichi Sekizuka, Makoto Suematsu

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Although the brain generates NO and carbon monoxide (CO), it is unknown how these gases and their enzyme systems interact with each other to regulate cerebrovascular function. We examined whether CO produced by heme oxygenase (HO) modulates generation and action of constitutive NO in the rat pial microcirculation. Immunohistochemical analyses indicated that HO-2 occurred in neurons and arachnoid trabecular cells, where NO synthase 1 (NOS1) was detectable, and also in vascular endothelium-expressing NOS3, suggesting colocalization of CO- and NO-generating sites. Intravital microscopy using a closed cranial window preparation revealed that blockade of the HO activity by zinc protoporphyrin IX significantly dilates arterioles. This vasodilatation depended on local NOS activities and was abolished by CO supplementation, suggesting that the gas derived from HO-2 tonically regulates NO-mediated vasodilatory response. Bioimaging of NO by laser-confocal microfluorography of diaminofluorescein indicated detectable amounts of NO at the microvascular wall, the subdural mesothelial cells, and arachnoid trabecular cells, which express NOS in and around the pial microvasculature. On CO inhibition by the HO inhibitor, regional NO formation was augmented in these cells. Such a pattern of accelerated NO formation depended on NOS activities and was again attenuated by the local CO supplementation. Studies using cultured porcine aortic endothelial cells suggested that the inhibitory action of CO on NOS could result from the photo-reversible gas binding to the prosthetic heme. Collectively, CO derived from HO-2 appears to serve as a tonic vasoregulator antagonizing NO-mediated vasodilatation in the rat cerebral microcirculation.

Original languageEnglish
JournalCirculation Research
Volume97
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Fingerprint

Carbon Monoxide
Microcirculation
Vasodilation
Heme Oxygenase (Decyclizing)
Arachnoid
Gases
heme oxygenase-2
Vascular Endothelium
Arterioles
Microvessels
Heme
Nitric Oxide Synthase
Lasers
Swine
Endothelial Cells
Neurons
Brain
Enzymes

Keywords

  • Carbon monoxide
  • Diaminofluorescein
  • Heme oxygenase
  • Nitric oxide
  • NO synthase vascular tone

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Carbon monoxide from heme oxygenase-2 is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation. / Ishikawa, Mami; Kajimura, Mayumi; Adachi, Takeshi; Maruyama, Kayo; Makino, Nobuya; Goda, Nobuhito; Yamaguchi, Tokio; Sekizuka, Eiichi; Suematsu, Makoto.

In: Circulation Research, Vol. 97, No. 12, 12.2005.

Research output: Contribution to journalArticle

Ishikawa, Mami ; Kajimura, Mayumi ; Adachi, Takeshi ; Maruyama, Kayo ; Makino, Nobuya ; Goda, Nobuhito ; Yamaguchi, Tokio ; Sekizuka, Eiichi ; Suematsu, Makoto. / Carbon monoxide from heme oxygenase-2 is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation. In: Circulation Research. 2005 ; Vol. 97, No. 12.
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AU - Ishikawa, Mami

AU - Kajimura, Mayumi

AU - Adachi, Takeshi

AU - Maruyama, Kayo

AU - Makino, Nobuya

AU - Goda, Nobuhito

AU - Yamaguchi, Tokio

AU - Sekizuka, Eiichi

AU - Suematsu, Makoto

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AB - Although the brain generates NO and carbon monoxide (CO), it is unknown how these gases and their enzyme systems interact with each other to regulate cerebrovascular function. We examined whether CO produced by heme oxygenase (HO) modulates generation and action of constitutive NO in the rat pial microcirculation. Immunohistochemical analyses indicated that HO-2 occurred in neurons and arachnoid trabecular cells, where NO synthase 1 (NOS1) was detectable, and also in vascular endothelium-expressing NOS3, suggesting colocalization of CO- and NO-generating sites. Intravital microscopy using a closed cranial window preparation revealed that blockade of the HO activity by zinc protoporphyrin IX significantly dilates arterioles. This vasodilatation depended on local NOS activities and was abolished by CO supplementation, suggesting that the gas derived from HO-2 tonically regulates NO-mediated vasodilatory response. Bioimaging of NO by laser-confocal microfluorography of diaminofluorescein indicated detectable amounts of NO at the microvascular wall, the subdural mesothelial cells, and arachnoid trabecular cells, which express NOS in and around the pial microvasculature. On CO inhibition by the HO inhibitor, regional NO formation was augmented in these cells. Such a pattern of accelerated NO formation depended on NOS activities and was again attenuated by the local CO supplementation. Studies using cultured porcine aortic endothelial cells suggested that the inhibitory action of CO on NOS could result from the photo-reversible gas binding to the prosthetic heme. Collectively, CO derived from HO-2 appears to serve as a tonic vasoregulator antagonizing NO-mediated vasodilatation in the rat cerebral microcirculation.

KW - Carbon monoxide

KW - Diaminofluorescein

KW - Heme oxygenase

KW - Nitric oxide

KW - NO synthase vascular tone

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