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Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2570-6. doi: 10.1161/ATVBAHA.111.229039.

Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules.

Author information

1
Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece.

Abstract

OBJECTIVE:

Carbon monoxide (CO) is a weak soluble guanylyl cyclase stimulator, leading to transient increases in cGMP and vasodilation. The aim of the present work was to measure the effect of CO-releasing molecules (CORMs) on the cGMP/nitric oxide (NO) pathway and to evaluate how selected CORMs affect NO-induced vasorelaxation.

METHODS AND RESULTS:

Incubation of smooth muscle cells with some but not all of the CORMs caused a minor increase in cGMP levels. Concentration-response curves were bell-shaped, with higher CORMs concentrations producing lower increases in cGMP levels. Although exposure of cells to CORM-2 enhanced cGMP formation, we observed that the compound inhibited NO-stimulated cGMP accumulation in cells and NO-stimulated soluble guanylyl cyclase activity that could be reversed by superoxide anion scavengers. Reactive oxygen species generation from CORMs was confirmed using luminol-induced chemiluminescence and electron spin resonance. Furthermore, we observed that NO is scavenged by CORM-2. When used alone CORM-2 relaxed vessels through a cGMP-mediated pathway but attenuated NO donor-stimulated vasorelaxation.

CONCLUSION:

We conclude that the CORMs examined have context-dependent effects on vessel tone, as they can directly dilate blood vessels, but also block NO-induced vasorelaxation.

PMID:
21836072
DOI:
10.1161/ATVBAHA.111.229039
[Indexed for MEDLINE]

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