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Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice
Citation:
Kurhanewicz, N., R. McIntosh-Kastrinsky, A. Ledbetter, L. Walsh, A. Farraj, AND M. Hazari. Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
Impact/Purpose:
This work examines the cardiovascular effects of a NAAQS pollutant (ozone) and a HAP (acrolein) in mice. It addresses Agency needs in the assessment of the effects of these pollutants and provides mechanistic information which will aid in the risk assessment process.
Description:
The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes heart rate variability (HRV) changes indicative of increased cardiovascular risk. HRV is an indicator of autonomic influence on the heart and represents homeostatic control mechanisms that operate dynamically to regulate cardiovascular function. Our previous data showed that a single exposure to acrolein or ozone causes decrements in cardiac mechanical function and dysrhythmia, which were found to be mediated by transient receptor potential cation channel A1 (TRPA1). Sensory activation through TRPA1 by air pollutants triggers autonomic reflexes so we hypothesized that exposure to acrolein or ozone would cause autonomic imbalance as demonstrated by changes in HRV. Conscious, unrestrained C57BL/6 (wt) and TRPA1 knockout (ko) mice were exposed to either 3ppm acrolein, 0.3ppm ozone or filtered air (FA) for 3 hours. Electrocardiogram (ECG) was recorded continuously before, during and after exposure. HRV was assessed 24 hours after exposure. HRV, which included the standard deviation of the NN intervals (SDNN), the root-mean-square of the successive differences between adjacent NNs (RMSSD) and the low frequency/high frequency (LF/HF) ratio, was increased independent of HR in wt mice during acrolein exposure. Interestingly, ozone did not cause any HRV changes in wt mice. There was no difference in the HRV of ko mice exposed to either acrolein or ozone when compared to FA. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance, which may represent a shift towards parasympathetic influence due to sensory irritation. Furthermore, although ozone also causes cardiac effects through TRPA1, it appears to do so independently of HRV-related autonomic mechanisms.(This abstract does not reflect EPA policy)