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

Antonia Marazioti, Mariarosaria Bucci, Ciro Coletta, Valentina Vellecco, Padmamalini Baskaran, Csaba Szabó, Giuseppe Cirino, Ana Rita Marques, Bruno Guerreiro, Ana M.L. Gonçalves, João D. Seixas, Annie Beuve, Carlos C. Romão, Andreas Papapetropoulos

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2570-2576
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2011

Keywords

  • cGMP
  • carbon monoxide
  • nitric oxide
  • pharmacology
  • vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Marazioti, A., Bucci, M., Coletta, C., Vellecco, V., Baskaran, P., Szabó, C., Cirino, G., Marques, A. R., Guerreiro, B., Gonçalves, A. M. L., Seixas, J. D., Beuve, A., Romão, C. C., & Papapetropoulos, A. (2011). Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules. Arteriosclerosis, thrombosis, and vascular biology, 31(11), 2570-2576. https://doi.org/10.1161/ATVBAHA.111.229039