title: Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans.
abstract: Fine particulate matter air pollution plus ozone impairs vascular function and raises diastolic blood pressure. We aimed to determine the mechanism and air pollutant responsible. The effects of pollution on heart rate variability, blood pressure, biomarkers, and brachial flow-mediated dilatation were determined in 2 randomized, double-blind, crossover studies. In Ann Arbor, 50 subjects were exposed to fine particles (150 microg/m(3)) plus ozone (120 parts per billion) for 2 hours on 3 occasions with pretreatments of an endothelin antagonist (Bosentan, 250 mg), antioxidant (Vitamin C, 2 g), or placebo. In Toronto, 31 subjects were exposed to 4 different conditions (particles plus ozone, particles, ozone, and filtered air). In Toronto, diastolic blood pressure significantly increased (2.9 and 3.6 mm Hg) only during particle-containing exposures in association with particulate matter concentration and reductions in heart rate variability. Flow-mediated dilatation significantly decreased (2.0% and 2.9%) only 24 hours after particle-containing exposures in association with particulate matter concentration and increases in blood tumor necrosis factor alpha. In Ann Arbor, diastolic blood pressure significantly similarly increased during all of the exposures (2.5 to 4.0 mm Hg), a response not mitigated by pretreatments. Flow-mediated dilatation remained unaltered. Particulate matter, not ozone, was responsible for increasing diastolic blood pressure during air pollution inhalation, most plausibly by instigating acute autonomic imbalance. Only particles from urban Toronto additionally impaired endothelial function, likely via slower proinflammatory pathways. Our findings demonstrate credible mechanisms whereby fine particulate matter could trigger acute cardiovascular events and that aspects of exposure location may be an important determinant of the health consequences.
authors.affiliation: University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48106, USA. robdbrok@umich.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Bruce
authors.initials: B
authors.lastname: Urch
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Dvonch
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bard
authors.forename: Mary
authors.initials: M
authors.lastname: Speck
authors.forename: Gerald
authors.initials: G
authors.lastname: Keeler
authors.forename: Masako
authors.initials: M
authors.lastname: Morishita
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Marsik
authors.forename: Ali S
authors.initials: AS
authors.lastname: Kamal
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
authors.forename: Jack
authors.initials: J
authors.lastname: Harkema
authors.forename: Paul
authors.initials: P
authors.lastname: Corey
authors.forename: Frances
authors.initials: F
authors.lastname: Silverman
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.forename: Greg
authors.initials: G
authors.lastname: Wellenius
authors.forename: Murray A
authors.initials: MA
authors.lastname: Mittleman
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brook
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000397:Air Pollution / Q000032:analysis*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D015716:Electrocardiography, Ambulatory; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis; D008297:Male; D010083:Oxidants, Photochemical / Q000494:pharmacology; D010126:Ozone / Q000494:pharmacology*; D052638:Particulate Matter / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D010083:Oxidants, Photochemical; D052638:Particulate Matter; D010126:Ozone