Long-Term Effects of Aircraft Noise Exposure on Vascular Oxidative Stress, Endothelial Function and Blood Pressure: No Evidence for Adaptation or Tolerance Development

Abstract

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure. C57BL/6J mice were exposed to aircraft noise for 0, 4, 7, 14 and 28d at a mean sound pressure level of 72 dB(A) and peak levels of 85 dB(A). Chronic aircraft noise exposure up to 28d caused persistent endothelial dysfunction and elevation of blood pressure. Likewise, reactive oxygen species (ROS) formation as determined by dihydroethidium (DHE) staining and HPLC-based measurement of superoxide formation in the aorta/heart/brain was time-dependently increased by noise. Oxidative burst in the whole blood showed a maximum at 4d or 7d of noise exposure. Increased superoxide formation in the brain was mirrored by a downregulation of neuronal nitric oxide synthase (Nos3) and transcription factor Foxo3 genes, whereas Vcam1 mRNA, a marker for inflammation was upregulated in all noise exposure groups. Induction of a pronounced hearing loss in the mice was excluded by auditory brainstem response audiometry. Endothelial dysfunction and inflammation were present during the entire 28d of aircraft noise exposure. ROS formation gradually increases with ongoing exposure without significant adaptation or tolerance in mice in response to chronic noise stress at moderate levels. These data further illustrate health side effects of long-term noise exposure and further strengthen a consequent implementation of the WHO noise guidelines in order to prevent the development of noise-related future cardiovascular disease.

Vascular Redox Signaling, Endothelial Nitric Oxide Synthase Uncoupling, and Endothelial Dysfunction in the Setting of Transportation Noise Exposure or Chronic Treatment with Organic Nitrates

“…Nitrate-tolerant animals and patients take profit from AT 1 -receptor blockade (Hirai et al, 2003 ; Knorr et al, 2011 ) and angiotensin-converting enzyme (ACE) inhibitor (Berkenboom et al, 1999 ; Heitzer et al, 1998 ; Watanabe et al, 1998 ) therapy. Similar observations were made in noise exposure animal studies, where RAAS activation was prominent as documented by elevated angiotensin-II levels (Munzel et al, 2017a ), additive damage of noise in mice with arterial hypertension by angiotensin-II infusion (Steven et al, 2020 ), and normalization of elevated blood pressure in noise-exposed mice by the ACE inhibitor captopril (Frenis et al, 2021b ). Although the molecular mechanisms of RAAS activation and increased ROS production are likely different in response to chronic nitrate therapy and noise exposure, the downstream health side effects on the cardiovascular system are likely the same (see summarizing scheme in Fig.…”

Transportation Noise Pollution and Cardiovascular Health

“…To test whether chronic exposure to aircraft noise results in noise habituation, we exposed animals to noise for up to 28 days, revealing persistent endothelial dysfunction and elevated blood pressure. 114 Additionally, there was a time-dependent increase in the formation of ROS, as observed through dihydroethidium staining and HPLCbased superoxide measurements in the aorta, heart, and brain. The oxidative burst in whole blood peaked after 4 to 7 days of noise exposure.…”

“…The formation of ROS increased gradually with ongoing exposure, indicating that mice did not habituate to chronic noise stress at moderate levels. 114 Noise Preconditioning and MI A significant clinical question concerns whether the side effects of noise are aggravated in susceptible patients, for example, patients with acute coronary syndromes. We addressed this by exposing mice to an average sound pressure level of 72 dB and a peak level of 85 dB for up to 4 days, activating proinflammatory aortic gene expression related to myeloid cell adhesion and diapedesis pathways.…”

“…The formation of ROS increased gradually with ongoing exposure, indicating that mice did not habituate to chronic noise stress at moderate levels. 114…”

Environmental Impacts on Cardiovascular Health and Biology: An Overview

“…Early studies in nonhuman primates and rodents showed that chronic noise exposure (4 weeks to 9 months) causes persistent increases in blood pressure, 66,67 which has been linked to impaired vascular reactivity and endothelium-dependent relaxation. 68 Studies in mice have also shown that aircraft noise exposure triggers endothelial dysfunction and vascular inflammation due to oxidative stress, and increased activation and adhesion of leukocytes, [69][70][71] which in turn can promote atherosclerosis. Another key pathway through which noise is thought to impair cardiovascular health is sleep disturbance.…”