Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium-dependent relaxation

Randa Zakhary, Sean P. Gaine, Jay L. Dinerman, Martial Ruat, Nicholas Flavahan, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with ≃10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.

Original languageEnglish (US)
Pages (from-to)795-798
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

Fingerprint

Endothelium
Carbon Monoxide
Nitric Oxide Synthase
Blood Vessels
Autonomic Ganglia
Nodose Ganglion
Myenteric Plexus
Adventitia
Superior Cervical Ganglion
Nitric Oxide Synthase Type III
Autonomic Nervous System
Ganglia
Pulmonary Artery
Intestines
Swine
Endothelial Cells
Immunohistochemistry
Neurons
Enzymes
heme oxygenase-2

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Heme oxygenase 2 : Endothelial and neuronal localization and role in endothelium-dependent relaxation. / Zakhary, Randa; Gaine, Sean P.; Dinerman, Jay L.; Ruat, Martial; Flavahan, Nicholas; Snyder, Solomon H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 2, 23.01.1996, p. 795-798.

Research output: Contribution to journalArticle

@article{e1ddd31fe7544930bdb46705ac7fc3b4,
title = "Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium-dependent relaxation",
abstract = "Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with ≃10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.",
author = "Randa Zakhary and Gaine, {Sean P.} and Dinerman, {Jay L.} and Martial Ruat and Nicholas Flavahan and Snyder, {Solomon H}",
year = "1996",
month = "1",
day = "23",
doi = "10.1073/pnas.93.2.795",
language = "English (US)",
volume = "93",
pages = "795--798",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2",

}

TY - JOUR

T1 - Heme oxygenase 2

T2 - Endothelial and neuronal localization and role in endothelium-dependent relaxation

AU - Zakhary, Randa

AU - Gaine, Sean P.

AU - Dinerman, Jay L.

AU - Ruat, Martial

AU - Flavahan, Nicholas

AU - Snyder, Solomon H

PY - 1996/1/23

Y1 - 1996/1/23

N2 - Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with ≃10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.

AB - Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with ≃10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.

UR - http://www.scopus.com/inward/record.url?scp=0030051948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030051948&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.2.795

DO - 10.1073/pnas.93.2.795

M3 - Article

C2 - 8570637

AN - SCOPUS:0030051948

VL - 93

SP - 795

EP - 798

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2

ER -