Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide

Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases. Cultured SMCs from rat aorta...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 1995-05, Vol.91 (9), p.2306-2309
Hauptverfasser: CHRISTODOULIDES, N, DURANTE, W, KROLL, M. H, SCHAFER, A. I
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container_end_page 2309
container_issue 9
container_start_page 2306
container_title Circulation (New York, N.Y.)
container_volume 91
creator CHRISTODOULIDES, N
DURANTE, W
KROLL, M. H
SCHAFER, A. I
description Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases. Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP. These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.
doi_str_mv 10.1161/01.cir.91.9.2306
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Psychology</topic><topic>Guanylate Cyclase - biosynthesis</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Heme - metabolism</topic><topic>Heme Oxygenase (Decyclizing) - analysis</topic><topic>Hemin - pharmacology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Rats</topic><topic>Sodium Compounds - pharmacology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHRISTODOULIDES, N</creatorcontrib><creatorcontrib>DURANTE, W</creatorcontrib><creatorcontrib>KROLL, M. H</creatorcontrib><creatorcontrib>SCHAFER, A. 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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete
subjects Animals
Aorta - metabolism
Arsenites - pharmacology
Biological and medical sciences
Blood Platelets - drug effects
Blood Platelets - metabolism
Blood vessels and receptors
Blotting, Western
Carbon Monoxide - metabolism
Cells, Cultured
Culture Media, Conditioned
Fundamental and applied biological sciences. Psychology
Guanylate Cyclase - biosynthesis
Guanylate Cyclase - metabolism
Heme - metabolism
Heme Oxygenase (Decyclizing) - analysis
Hemin - pharmacology
Muscle, Smooth, Vascular - metabolism
Rats
Sodium Compounds - pharmacology
Vertebrates: cardiovascular system
title Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide
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