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Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules
- Publication Year :
- 2011
-
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.
- Subjects :
- Male
Vasodilation
Nitric Oxide
Muscle, Smooth, Vascular
law.invention
Nitric oxide
chemistry.chemical_compound
law
Animals
Rats, Wistar
Cyclic GMP
Incubation
Aorta
Cells, Cultured
Chemiluminescence
Carbon Monoxide
Dose-Response Relationship, Drug
Superoxide
Carbon monoxide-releasing molecules
Rats
chemistry
Biochemistry
Guanylate Cyclase
Models, Animal
Biophysics
Reactive Oxygen Species
Cardiology and Cardiovascular Medicine
Soluble guanylyl cyclase
Signal Transduction
Carbon monoxide
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....bffc7e6aa1564940b73bd83c0664dcd9