title: The influence of Nrf2 on cardiac responses to environmental stressors.
abstract: Nrf2 protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role of Nrf2 on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption of Nrf2 would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures. Nrf2(-/-) and Nrf2(+/+) 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) in Nrf2(-/-) mice compared to Nrf2(+/+) mice. Nrf2(-/-) mice tolerated hyperoxia significantly less than Nrf2(+/+) mice (~22 hrs; P < 0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater in Nrf2(-/-) compared to Nrf2(+/+) mice (P < 0.01). Results demonstrate that Nrf2 deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations.
authors.affiliation: Laboratory of Systems Physiology, Department of Kinesiology, University of North Carolina at Charlotte, Charlotte, NC, USA. rhowden@uncc.edu
authors.forename: Reuben
authors.initials: R
authors.lastname: Howden
authors.forename: Eva
authors.initials: E
authors.lastname: Gougian
authors.forename: Marcus
authors.initials: M
authors.lastname: Lawrence
authors.forename: Samantha
authors.initials: S
authors.lastname: Cividanes
authors.forename: Wesley
authors.initials: W
authors.lastname: Gladwell
authors.forename: Laura
authors.initials: L
authors.lastname: Miller-DeGraff
authors.forename: Page H
authors.initials: PH
authors.lastname: Myers
authors.forename: D Clay
authors.initials: DC
authors.lastname: Rouse
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.forename: Hye-Youn
authors.initials: HY
authors.lastname: Cho
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004777:Environment; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D018496:Hyperoxia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D052638:Particulate Matter