title: Involvement of Heme Oxygenase-1 in particulate matter-induced impairment of NO-dependent relaxation in rat intralobar pulmonary arteries.
abstract: Particulate air pollution exerts deleterious effects on cardiovascular system. We previously described that exposure to urban particulate matter (SRM1648) impairs nitric oxide (NO, a major vasculoprotective factor) responsiveness in intrapulmonary arteries. As Heme Oxygenase-1 (HO-1) is induced by urban particles in some cell types and is known to alter NO-dependent signaling pathway, the objective was to characterize HO-1 involvement in SRM1648-induced impairment of NO-dependent relaxation in intrapulmonary arteries. Rat intrapulmonary artery rings were exposed or not to Co (III) Protoporphyrin IX Chloride (HO-1 inducer) or SRM1648 in the absence or presence of Cr (III) Mesoporphyrin IX Chloride (HO-1 activity inhibitor). NO-dependent relaxation was assessed with DEA-NOnoate (DEA-NO) on pre-contracted arteries. HO-1 and soluble guanylyl-cyclase (sGC) mRNA and protein expressions were assessed by qRT-PCR and Western blotting, respectively. SRM1648 or Co (III) Protoporphyrin IX Chloride exposure (24) impaired DEA-NO-dependent relaxation. The SRM-induced alteration of DEA-NO responsiveness was partially prevented by Cr (III) Mesoporphyrin IX Chloride. Co (III) Protoporphyrin IX Chloride induced HO-1 mRNA and protein expressions, whereas SRM1648 only induced HO-1 protein expression without affecting its mRNA level. Exposure to either SRM1648 or to Co (III) Protoporphyrin IX Chloride did not affect the expression levels of sGC. In conclusion, this study provides some evidence that impairment of NO signaling pathway in intrapulmonary arteries involves HO-1. Therefore it highlights the role of HO-1 in particulate matter-induced detrimental effects in pulmonary circulation.
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Barrier
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Bégorre
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baudrimont
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Freund-Michel
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France; CHU de Bordeaux, Bordeaux, F-33076, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
authors.affiliation: Université de Bordeaux, Bordeaux F-33076, France; Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux F-33076, France; CHU de Bordeaux, Bordeaux, F-33076, France. Electronic address: arnaud.courtois@u-bordeaux.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Courtois
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D052638:Particulate Matter / Q000633:toxicity*; D011524:Protoporphyrins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D017208:Rats, Wistar; D014664:Vasodilation
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D011524:Protoporphyrins; D009569:Nitric Oxide; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Heme Oxygenase-1; Nitric oxide; Particulate matter; Pulmonary artery