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

Antonia Marazioti, Mariarosaria Bucci, Ciro Coletta, Valentina Vellecco, Padmamalini Baskaran, Csaba Szabo, 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 Citations (Scopus)

    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 2011

    Fingerprint

    Carbon Monoxide
    Vasodilation
    Nitric Oxide
    Luminol
    Nitric Oxide Donors
    Electron Spin Resonance Spectroscopy
    Luminescence
    Superoxides
    Smooth Muscle Myocytes
    Blood Vessels
    Reactive Oxygen Species

    Keywords

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

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules. / Marazioti, Antonia; Bucci, Mariarosaria; Coletta, Ciro; Vellecco, Valentina; Baskaran, Padmamalini; Szabo, Csaba; Cirino, Giuseppe; Marques, Ana Rita; Guerreiro, Bruno; Gonçalves, Ana M L; Seixas, João D.; Beuve, Annie; Romão, Carlos C.; Papapetropoulos, Andreas.

    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 31, No. 11, 11.2011, p. 2570-2576.

    Research output: Contribution to journalArticle

    Marazioti, A, Bucci, M, Coletta, C, Vellecco, V, Baskaran, P, Szabo, C, Cirino, G, Marques, AR, Guerreiro, B, Gonçalves, AML, Seixas, JD, Beuve, A, Romão, CC & Papapetropoulos, A 2011, 'Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 11, pp. 2570-2576. https://doi.org/10.1161/ATVBAHA.111.229039
    Marazioti, Antonia ; Bucci, Mariarosaria ; Coletta, Ciro ; Vellecco, Valentina ; Baskaran, Padmamalini ; Szabo, Csaba ; Cirino, Giuseppe ; Marques, Ana Rita ; Guerreiro, Bruno ; Gonçalves, Ana M L ; Seixas, João D. ; Beuve, Annie ; Romão, Carlos C. ; Papapetropoulos, Andreas. / Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2011 ; Vol. 31, No. 11. pp. 2570-2576.
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    AU - Baskaran, Padmamalini

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    AU - Guerreiro, Bruno

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