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
