1. Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules
- Author
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Ana R. Marques, Giuseppe Cirino, Annie Beuve, Mariarosaria Bucci, Ciro Coletta, Csaba Szabó, Carlos C. Romão, Valentina Vellecco, João Seixas, Andreas Papapetropoulos, Ana M. L. Gonçalves, Bruno Guerreiro, Antonia Marazioti, Padmamalini Baskaran, Marazioti, A, Bucci, Mariarosaria, Coletta, C, Vellecco, Valentina, Baskaran, P, Szabó, C, Cirino, Giuseppe, Marques, Ar, Guerreiro, B, Gonçalves, Am, Seixas, Jd, Beuve, A, Romão, Cc, and Papapetropoulos, A.
- 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 - 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.
- Published
- 2011