title: Effects of concentrated fine ambient particles on rat plasma levels of asymmetric dimethylarginine.
abstract: The health effects of ambient fine particulate matter (PM(2.5)) and its potential impact on vascular endothelial function have not been thoroughly investigated. As endothelial dysfunction plays an important role in the pathogenesis of atherosclerosis and its complications, we examined the effects of concentrated fine ambient particles (CAPs) on the plasma level of asymmetric dimethylarginine (ADMA) in a pilot study. ADMA is a circulating endogenous inhibitor of nitric oxide synthase (NOS) that is associated with impaired vascular function and increased risk for cardiovascular events. A mobile air research laboratory (AirCARE 1) was used to provide "real-world" CAPs exposures for this study conducted in Detroit, MI. Fourteen Brown Norway rats were exposed to filtered air (FA) (n = 7) or CAPs (0.1-2.5 microm) (n = 7) for 3 consecutive days (8 h/day) in July 2002. Rats were exposed during these periods to average particle mass concentrations of 354 microg/m(3). Rat plasma samples were collected 24 h postexposure. Plasma concentrations of ADMA were significantly elevated in rats exposed to CAPs versus those exposed to FA (mean +/- standard deviation = 1.49 +/- 0.18 vs. 1.29 +/- 0.26 microM, p =.05 by one-tailed t-test). Analyses of meteorological data and CAPs trace element composition suggest that local particle emission sources contributed largely to overall mass of CAPs. Results of this pilot study suggest that exposure to PM(2.5) at high concentrations may trigger an acute increase in circulating ADMA level. This finding has implications for the regulation of vasomotor tone by particulate pollutants and the propensity for adverse cardiovascular events.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, 48109-2029, USA. dvonch@umichedu
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Dvonch
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Keeler
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Louis G
authors.initials: LG
authors.lastname: D'Alecy
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Marsik
authors.forename: Masako
authors.initials: M
authors.lastname: Morishita
authors.forename: Fuyuen Y
authors.initials: FY
authors.lastname: Yip
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brook
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Timm
authors.forename: James G
authors.initials: JG
authors.lastname: Wagner
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001273:Atmosphere Exposure Chambers; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008685:Meteorological Concepts; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010316:Particle Size; D010865:Pilot Projects; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D000393:Air Pollutants; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase