title: The source of endogenous carbon monoxide formation in human placental chorionic villi.
abstract: Carbon monoxide (CO) is proposed to play a role in placental vascular control, as the placenta produces and responds to CO. The mechanism by which CO is formed by the placenta is unclear but could be through heme oxygenase (HO) degradation of heme, lipid peroxidation, or both. Human placental cotyledons were perfused with Kreb s solution to remove blood. Chorionic villi segments were prepared for measurements of CO production in the absence/presence of an exogenous supply of heme substrate (methemalbumin), inhibitors of HO, or inhibitors of lipid peroxidation. HO inhibitors used were chromium mesoporphyrin (CrMP) (0.1 mM, 0.3 mM), and azalanstat (0.1 mM, 0.3 mM). The lipid peroxidation inhibitors used were EDTA (0.1 mM, 0.3 mM) and deferoxamine (0.1 mM). Incubation of villi segments with methemalbumin (0.15 mM, 0.3 mM, 0.45 mM) resulted in a concentration-dependent increase in CO formation above the basal, endogenous rate. CrMP and azalanstat inhibited basal endogenous CO production, whereas EDTA and deferoxamine enhanced CO formation above basal level. These results demonstrate that endogenous CO was formed by human chorionic villi from heme, primarily through the action of HO, and are consistent with the hypothesis that HO plays a role in the regulation of placental vasculature by the formation of heme-derived CO.
authors.affiliation: Department of Pharmacology & Toxicology, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Ahmed
authors.forename: B E
authors.initials: BE
authors.lastname: McLaughlin
authors.forename: J
authors.initials: J
authors.lastname: Soong
authors.forename: G S
authors.initials: GS
authors.lastname: Marks
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: K
authors.initials: K
authors.lastname: Nakatsu
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism*; D002824:Chorionic Villi / Q000378:metabolism*; D005260:Female; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D021041:Placental Circulation; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)