title: Characterization of the components of urban particulate matter mediating impairment of nitric oxide-dependent relaxation in intrapulmonary arteries.
abstract: We have previously shown that exposure to urban particulate matter (UPM) impairs endothelial nitric oxide (NO) bioactivity in intrapulmonary arteries. As UPM is composed of heterogeneous constituents, the aim of this study was to clarify the class of pollutants responsible for such effect. Extracts (aqueous, acidic or organic) were prepared from SRM1648, an UPM sample collected in St. Louis (MO, USA). The metal composition of extracts as well as endotoxin content was determined. The effects of each extract, metal mixture and endotoxin were evaluated on endothelium-dependent relaxation to acetylcholine (reflecting endothelial NO production) in rat isolated intrapulmonary arteries. Aqueous or organic SRM1648 pretreatment altered acetylcholine-induced relaxation, similar to that induced by native SRM1648. Organic extract induced similar attenuation of acetylcholine relaxation than organic-treated SRM1648, whereas aqueous extract had no effect. Acidic pretreatment, which impoverished metal and endotoxin content of SRM1648, prevented the impairment of acetylcholine-induced relaxation. However, neither the acidic extract enriched in metals, nor a metal mixture representative of SRM1648 content, modified acetylcholine relaxation, while endotoxin impaired it. Polymyxin B, which chelates endotoxin, prevented SRM1648-induced decrease in relaxation to acetylcholine. It is concluded that SRM1648-induced impairment of endothelial NO-dependent relaxation in intrapulmonary arteries unlikely involved a soluble factor released by vascular cells during UPM exposure, but rather an organic extractible and acidic-sensitive constituents of UPM. Endotoxin, but not metals, may be responsible for UPM-induced impairment of endothelial NO-dependent relaxation.
authors.affiliation: Université Bordeaux Segalen, Bordeaux, F-33076, France; Inserm, U1045, Centre de Recherche Cardio-Thoracique, Bordeaux, F-33076, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Courtois
authors.forename: Caroline
authors.initials: C
authors.lastname: Prouillac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baudrimont
authors.forename: Céline
authors.initials: C
authors.lastname: Ohayon-Courtes
authors.forename: Véronique
authors.initials: V
authors.lastname: Freund-Michel
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.forename: Mariette
authors.initials: M
authors.lastname: Lisbonne-Autissier
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000032:analysis / Q000633:toxicity*; D008297:Male; D008670:Metals / Q000032:analysis / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017208:Rats, Wistar; D018570:Risk Assessment; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D008670:Metals; D052638:Particulate Matter; D014665:Vasodilator Agents; D009569:Nitric Oxide
keywords: Endothelium; NO; intrapulmonary artery; particulate matter extracts