Pretreatment with an antioxidant regimen increased vasoconstriction. - GreenMedInfo Summary

: Rationale/ Objectives: The model traffic-related air pollutant exposure, diesel exhaust inhalation, is associated with vascular dysfunction. We studied 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, 22 healthy adult participants were exposed in randomized, balanced order to exposure with diesel exhaust (200μg/m3 PM2.5) and filtered air and to pretreatment with antioxidants (N- acetyl cysteine and ascorbate) and placebo. Before and after each exposure, brachial artery diameter was assessed using ultrasound. Changes in brachial artery diameter 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.

MAIN RESULTS: Compared with filtered air, exposure to diesel exhaust resulted in a significant reduction in brachial artery diameter (mean -0.09mm, 95% CI -0.01, -0.17; p = 0.03). Pretreatment with antioxidants augmented diesel exhaust related vasoconstriction; participants pretreated with antioxidants had a diesel exhaust effect of -0.18mm (95%CI -0.28 to -0.07 mm; p = 0.01). Diesel exhaust related vasoconstriction was primarily observed in the variant alleles of AGTR1 and TRPV1.

CONCLUSION: We confirmed that short-term exposure to diesel exhaust in healthy participants is associated with 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. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00434005.