Diesel Exhaust Inhalation Elicits Acute Vasoconstriction in Vivo

The association between ambient fine particulate matter (PM) air pollution [particles with aerodynamic diameter ≤ 2.5 μm (PM2.5)] and increased cardiovascular morbidity and mortality in epidemiologic studies (Dominici et al. 2006; Miller et al. 2007; Pope et al. 2002) has led to investigation of underlying mechanisms, which remain cryptic (Bhatnagar 2006). Several studies link ambient (especially combustion-derived) PM with increased vascular tone (Brook et al. 2002; Campen et al. 2005; Proctor et al. 2006), and animal studies showed possible involvement of sympathetic nervous system activation (Proctor et al. 2006) and vasoconstriction pathways (Bouthillier et al. 1998; Li et al. 2005). Evidence suggests that the effect of PM on vascular reactivity may be greater in individuals at risk for coronary artery disease (O’Neill et al. 2005). Human studies to date have provided limited insight into the mechanism of the vascular effects of PM, although recent evidence has documented enhanced exercise-induced ischemia with controlled exposure to diesel exhaust (DE) (Mills et al. 2007). DE is a complex mixture of particulate and gaseous pollutants that comprise a substantial and biologically active fraction of urban ambient air pollution (Health Effects Institute 1995) and is a very appropriate experimental model exposure, especially with the current interest in traffic-related air pollution. Evidence suggests that inhalation of DE is associated with perturbation in endothelial function (Campen et al. 2005; Mills et al. 2005; Tornqvist et al. 2007). We exposed young adults, healthy or with metabolic syndrome, to DE under controlled settings. Young adults with metabolic syndrome have increased subclinical atherosclerosis (Tzou et al. 2005) and are at increased risk for cardiovascular morbidity and mortality (Isomaa et al. 2001). We focused on individuals with metabolic syndrome because they might be more susceptible to DE effects. We hypothesized that DE inhalation would result in vaso-constriction and decreased endothelium-dependent flow-mediated dilation (FMD) of the brachial artery within 30 min of exposure. We also hypothesized that vascular effects of DE might be related to activation of the sympathetic nervous system or increased release of the endothelium-dependent vasoconstrictor endothelin-1 (ET-1).