We have demonstrated for the first time that inhalation of common air pollutants affects the systemic vasculature of humans. Short-term exposure to PM2.5 and O3 at levels that occur in urban environments causes acute conduit artery vasoconstriction without producing immediate alterations in endothelial-dependent or -independent vasomotion. This finding is important because it suggests that alterations in arterial tone may be a relevant mechanism contributing to air pollution–mediated acute cardiac events and because it provides evidence that the observations shown by large epidemiological studies are biologically plausible.1
Relevance of Conduit Artery Vasoconstriction
It is reasonable to suspect that the coronary vasculature may respond similarly to air pollution exposure because brachial and coronary reactivity strongly correlate (r=0.79, P<0.001 for brachial versus coronary FMD).10 Even so, a reduction in coronary diameter of this relatively small magnitude (0.1 mm) would have minimal impact on healthy adults. However, congruent with epidemiological findings that individuals at increased risk for acute air pollution–related cardiac events generally have pre-existing cardiovascular disease, 2 this degree of sudden coronary vasoconstriction could promote cardiac ischemia in those with underlying flow-limiting obstructive lesions or could trigger instability of susceptible plaques.11 Furthermore, the vasculature of patients with coronary risk factors is known to hyper-react to a variety of vasoconstrictors,12,13 which potentially increases their susceptibility for acute cardiac events after air pollution exposure. Additional investigations in the coronary circulation and in high-risk individuals are needed to confirm these hypotheses.
Mechanisms and Mediators of Vasoconstriction
Because this is the first study to investigate the effects of air pollution on the vasculature, a more complete understanding of the pathophysiological mechanisms underlying our observations and the specific pollutants involved requires further investigation. Substantial evidence links increased PM2.5 alone with cardiac mortality.1 However, our initial air pollution exposure was chosen to be PM2.5 plus O3 because this mixture occurs in "real-life" settings. At present, an effect on the vasculature partially mediated by O3 cannot be ruled out. Determinations of the relative importance of PM2.5 versus O3 and specific components in fine particulate matter await follow-up studies now that a meaningful effect of urban air pollution on vascular function has been demonstrated.
Potential biological mechanisms for the vasoconstriction include a reflex increase in sympathetic nervous system activity via stimulation of pulmonary vagal afferents14 or an acute increase in vascular ET release, analogous to cigarette smoking.15 PM2.5 inhalation has been shown to induce systemic inflammation and cytokine production,16 possibly related to free radical activity of components in particulate matter.17 In turn, these have the capacity to enhance vascular ET expression by direct mechanisms or via activation of oxidative stress pathways.6 Indeed, we have previously demonstrated the presence of increased plasma ET levels acutely after PM2.5 exposure.5
In conclusion, alterations in arterial tone and reactivity in response to PM2.5 and O3 exposure is a new arena for future research into the biological mechanisms linking air pollution with acute and potentially chronic cardiovascular events. Further investigations are needed to confirm and extend our findings to the coronary circulation and to subjects with existing heart disease.