Aims: Aircraft noise exposure causes endothelial dysfunction, oxidative stress and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms are not well understood. Here we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise exposure protocols (around-the-clock, sleep vs. awake phase noise) on vascular and cerebral oxidative stress in mice.

Methods and Results: C57BL/6j and Nox2^-/- (gp91phox^-/-) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep respectively awake phases for 1, 2 and 4 days. Adverse effects of around-the-clock noise exposure on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise exposure of the mice lead to the most pronounced vascular effects and affected circadian clock as revealed by next generation sequencing, suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise exposure caused increased blood pressure, endothelial dysfunction, increased markers of oxidative stress and systemic inflammation. Noise also increased cerebral oxidative stress in the frontal cortex, in part mediated by endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein downregulation, nNOS Ser847 phosphorylation and Nox2 upregulation. In patients with established coronary artery disease, nighttime aircraft noise increased oxidative stress biomarkers in serum.

Conclusion: Aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce nighttime aircraft noise are warranted.