The Influence ofNrf2on Cardiac Responses to Environmental Stressors

Abstract

Nrf2protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role ofNrf2on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption ofNrf2would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures.Nrf2-/-andNrf2+/+mice were instrumented for continuous ECG recording to calculate HR and HRV (low frequency (LF), high frequency (HF), and total power (TP)). Mice were then either exposed to hyperoxia for up to 72 hrs or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P<0.001) and HF HRV (P<0.001) inNrf2-/-mice compared toNrf2+/+mice.Nrf2-/-mice tolerated hyperoxia significantly less thanNrf2+/+mice (~22 hrs;P<0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater inNrf2-/-compared toNrf2+/+mice (P<0.01). Results demonstrate thatNrf2deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations.