title: Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation.
abstract: Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter≤2.5 μm, PM2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated São Paulo city air PM2.5 at an accumulated daily dose of approximately 600 μg/m3. Pulmonary arteries isolated from PM2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-α was enhanced by PM2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (Emax) to acetylcholine. A negative correlation was found between vascular TNF-α expression and Emax to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-α level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM2.5.
authors.affiliation: Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, State University of Campinas-UNICAMP, Campinas, Brazil. anadavel@unicamp.br
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Davel
authors.forename: Miriam
authors.initials: M
authors.lastname: Lemos
authors.forename: Luciana Manfré
authors.initials: LM
authors.lastname: Pastro
authors.forename: Sibelli Cosme
authors.initials: SC
authors.lastname: Pedro
authors.forename: Paulo Afonso
authors.initials: PA
authors.lastname: de André
authors.forename: Cristina
authors.initials: C
authors.lastname: Hebeda
authors.forename: Sandra Helena
authors.initials: SH
authors.lastname: Farsky
authors.forename: Paulo Hilário
authors.initials: PH
authors.lastname: Saldiva
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase