Pretreatment with Antioxidants Augments the Acute Arterial Vasoconstriction Caused by Diesel Exhaust Inhalation

Abstract

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 mg/m 3 particulate matter with an aerodynamic diameter < 2.5 mm [PM 2.5 ]) 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. Conclusions: We confirmed that short-term exposure to diesel exhaust in healthy subjects 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.

Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution

“…Regrettably, these findings have not been replicated in human studies, with antioxidant-rich foods or supplements having inconsistent effects on PM 2.5 -induced heart rate variability (248,249) and vascular dysfunction (250–252). Of concern, and despite the fact that in chronic smokers vitamin C has been shown to improve endothelium-dependent forearm blood flow (252), in another study, the vasoconstrictor effects of DE were actually greater in volunteers receiving vitamin C or NAC (253), These findings mirror those of the largely negative results of large-scale antioxidant trials for CVD in general (254), and may reflect the inability of current compounds to reach and reduce oxidative stress at key biological areas. Nevertheless, the identification of individuals with polymorphisms of antioxidant genes as being particularly susceptible to the effects of air pollution (210) suggests that this avenue of research still deserves further attention in hypothesis-driven studies with long-term intervention.…”

Ambient Air Pollution and Clinical Implications for Susceptible Populations

“…Statins have been investigated in animal models and may attenuate the inflammatory effects of particulates, but evidence in humans is limited (43). Similarly, supplementation with dietary antioxidants has shown mixed results in attenuating the vascular effects of PM 2.5 and diesel exhaust exposure (44)(45)(46).…”

Personal strategies to minimise effects of air pollution on respiratory health: advice for providers, patients and the public

“…In a second study of similar design, pre-treatment with vitamin C and N-acetylcysteine augmented DEP-induced vasoconstriction [198]. Both studies observed a role for genetic variability in dictating responses to DEP exposure and antioxidant supplementation [197,198].…”

“…In healthy participants, pre-treatment with N-acetylcysteine diminished DEP-induced airway responsiveness in participants with baseline airway hyperresponsiveness [197]. In a second study of similar design, pre-treatment with vitamin C and N-acetylcysteine augmented DEP-induced vasoconstriction [198]. Both studies observed a role for genetic variability in dictating responses to DEP exposure and antioxidant supplementation [197,198].…”