Pretreatment with antioxidants augments the acute arterial vasoconstriction caused by diesel exhaust inhalation

Rationale: Diesel exhaust inhalation, which is the model trafficrelated air pollutant exposure, is associated with vascular dysfunction. Objectives: To determine whether healthy subjects exposed to diesel exhaust exhibit acute vasoconstriction and whether this effect could be modified by the use of antioxidants or by common variants in the angiotensin II type 1 receptor (AGTR1) and other candidate genes. Methods: In a genotype-stratified, double-blind, four-way crossover study, 21 healthy adult subjects were exposed at rest in a randomized, balanced order to diesel exhaust (200 μg/m³ particulate matter with an aerodynamic diameter ≤ 2.5 μm[PM2.5]) and filtered air, and to pretreatment with antioxidants (Nacetylcysteine and ascorbate) and placebo. Before and after each exposure, brachial artery diameter (BAd) was assessed using ultrasound. Changes in BAd were compared across pretreatment and exposure sessions. Gene-exposure interactions were evaluated in the AGTR1 A1166C polymorphism, on which recruitment was stratified, and other candidate genes, including TRPV1 and GSTM1. Measurements and Main Results: Compared with filtered air, exposure to diesel exhaust resulted in a significant reduction in BAd (mean, 20.09 mm, 95% confidence interval [CI], 20.01 to 20.17; P = 0.03). Pretreatment with antioxidants augmented diesel exhaust-related vasoconstriction with a mean change in BAd of 20.18 mm (95% CI, 20.28 to 20.07 mm; P = 0.001). Diesel exhaust-related vasoconstriction was primarily observed in the variant alleles of AGTR1 and TRPV1. No association was found between diesel exhaust inhalation and flow-mediated dilation. Conclusions: We confirmed that short-term exposure to diesel exhaust in healthy subjects is associatedwith acute vasoconstriction in a conductance artery and found suggestive evidence of involvement of nociception and renin-angiotensin systems in this effect. Pretreatment with an antioxidant regimen increased vasoconstriction.