Impact of ozone exposure on heart rate variability and stress hormones: A randomized-crossover study

The biological mechanisms underlying the associations between atmospheric ozone exposure and adverse cardiometabolic outcomes are yet to be identified. Imbalanced autonomic nervous system (ANS) as well as activations of the sympatho-adrenomedullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axes are among possible early biological responses triggered by ozone, and may eventually lead to cardiometabolic abnormalities. To determine whether acute ozone exposure causes ANS imbalance and increases the secretion of neuroendocrine stress hormones, we conducted a randomized, double-blind, crossover trial, under controlled 2-hour exposure to either ozone (200 ppb) or clean air with intermittent exercise among 22 healthy young adults. Here we found that, compared to clean air exposure, acute ozone exposure significantly decreased the high-frequency band of heart rate variability, even after adjusting for heart rate and pre-exposure to ambient air pollutants and meteorological factors. Ozone exposure also significantly increased the serum levels of stress hormones, including corticotrophin-releasing factor, adrenocorticotropic hormone, adrenaline, and noradrenaline. Metabolomics analysis showed that acute ozone exposure led to alterations in stress hormones, systemic inflammation, oxidative stress, and energy metabolism. Our results suggest that acute ozone exposure may trigger ANS imbalance and activate the HPA and SAM axes, offering potential biological explanations for the adverse cardiometabolic effects following acute ozone exposure.