title: Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor.
abstract: Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates inflammation and vascular function. We investigated the acute effects of St. Louis, Missouri, urban particles (UPs; Standard Reference Material 1648) on the constriction of isolated rat pulmonary artery rings and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) in human pulmonary artery endothelial cells with or without losartan, an antagonist of AT1R. UPs at 1-100 microg/mL induced acute vasoconstriction in pulmonary artery. UPs also produced a time- and dose-dependent increase in phosphorylation of ERK1/2 and p38 MAPK. Losartan pretreatment inhibited both the vasoconstriction and the activation of ERK1/2 and p38. The water-soluble fraction of UPs was sufficient for inducing ERK1/2 and p38 phosphorylation, which was also losartan inhibitable. Copper and vanadium, two soluble transition metals contained in UPs, induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38, but only the phosphorylation of p38 was inhibited by losartan. The UP-induced activation of ERK1/2 and p38 was attenuated by captopril, an angiotensin-converting enzyme inhibitor. These results indicate that activation of the local renin-angiotensin system may play an important role in cardiovascular effects induced by PM.
authors.affiliation: Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Li
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Carter
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Dailey
authors.forename: Yuh-Chin T
authors.initials: YC
authors.lastname: Huang
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D002478:Cells, Cultured; D002947:Cities; D003300:Copper / Q000494:pharmacology; D004391:Dust; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008923:Missouri; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014639:Vanadium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D004391:Dust; D044140:Receptor, Angiotensin, Type 1; D014639:Vanadium; D003300:Copper; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D019808:Losartan