title: Effects of carbon monoxide-releasing molecules on pulmonary vasoreactivity in isolated perfused lungs.
abstract: In addition to its renowned poisonous effects, carbon monoxide (CO) is being recognized for its beneficial actions on inflammatory and vasoregulatory pathways, particularly when applied at low concentrations via CO-releasing molecules (CO-RMs). In the lung, CO gas and CO-RMs are suggested to decrease pulmonary vascular tone and hypoxic pulmonary vasoconstriction (HPV). However, the direct effect of CO-RMs on the pulmonary vasoreactivity in isolated lungs has not yet been investigated. We assessed the effect of CORM-2 and CORM-3 on the pulmonary vasculature during normoxia and acute hypoxia (1% oxygen for 10 min) in isolated ventilated and perfused mouse lungs. The effects were compared with those of inhaled CO gas (10%). The interaction of CORM-2 or CO with cytochrome P-450 (CYP) was measured simultaneously by tissue spectrophotometry. Inhaled CO decreased HPV and vasoconstriction induced by the thromboxane mimetic U-46619 but did not alter KCl-induced vasoconstriction. In contrast, concentrations of CORM-2 and CORM-3 used to elicit beneficial effects on the systemic circulation did not affect pulmonary vascular tone. High concentration of CO-RMs or long-term application induced a continuous increase in normoxic pressure. Inhaled CO showed spectral alterations correlating with the inhibition of CYP. In contrast, during application of CORM-2 spectrophotometric signs of interaction with CYP could not be detected. Application of CO-RMs in therapeutic doses in isolated lungs neither decreases pulmonary vascular tone and HPV nor does it induce spectral alterations that are characteristic of CO-inhibited CYP. High doses, however, may cause pulmonary vasoconstriction.
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Oleg
authors.identifier: http://orcid.org/0000-0002-9733-3690
authors.initials: O
authors.lastname: Pak
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and Faculty of Pharmacy, Department of Pharmacology & Toxicology, Al-Azhar University, Assiut, Egypt.
authors.forename: Adel G
authors.initials: AG
authors.lastname: Bakr
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Mareike
authors.initials: M
authors.lastname: Gierhardt
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Julia
authors.initials: J
authors.lastname: Albus
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Ievgen
authors.initials: I
authors.lastname: Strielkov
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Kroschel
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Timm
authors.initials: T
authors.lastname: Hoeres
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hecker
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and Norbert.Weissmann@innere.med.uni-giessen.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center, Justus-Liebig-University, Giessen, Member of the German Center for Lung Research (DZL), Germany; and.
authors.forename: Natascha
authors.initials: N
authors.lastname: Sommer
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); C447082:tricarbonyldichlororuthenium (II) dimer; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002248:Carbon Monoxide
keywords: carbon monoxide; carbon monoxide-releasing molecule-2; carbon monoxide-releasing molecule-3; hypoxic pulmonary vasoconstriction