title: Inhibition of nitric oxide-stimulated vasorelaxation by carbon monoxide-releasing molecules.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Marazioti
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Bucci
authors.forename: Ciro
authors.initials: C
authors.lastname: Coletta
authors.forename: Valentina
authors.initials: V
authors.lastname: Vellecco
authors.forename: Padmamalini
authors.initials: P
authors.lastname: Baskaran
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Marques
authors.forename: Bruno
authors.initials: B
authors.lastname: Guerreiro
authors.forename: Ana M L
authors.initials: AM
authors.lastname: Gonçalves
authors.forename: João D
authors.initials: JD
authors.lastname: Seixas
authors.forename: Annie
authors.initials: A
authors.lastname: Beuve
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Romão
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP