Citation:

Kurhanewicz, N., A. Ledbetter, A. Farraj, AND M. Hazari. TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 347:104-114, (2018). https://doi.org/10.1016/j.taap.2018.03.027

Impact/Purpose:

The purpose of this study was to determine the mechanisms through which acrolein, a ubiquitous air pollutant, causes cardiovascular dysfunction in mice. It verifies that cardiac susceptibility to air pollution may be mediated by autonomic imbalance.

Description:

This study describes the effects of inhaled acrolein on the cardiac function of normal and TRPA1 knockout mice. The data suggest that cardiac autonomic imbalance and arrhythmia due to exposure are mediated by TRPA1, an irritant sensor, and subsequent autonomic changes that render the host susceptible. Numerous studies have demonstrated that short-term air pollution exposure causes cardiac autonomic imbalance as measured by heart rate variability (HRV). We previously showed that a single exposure to acrolein, a ubiquitous gaseous component of air pollution, not only causes autonomic imbalance, but also increases arrhythmia through transient receptor potential A1 (TRPA1) cation channels. Thus, the goal of this study was to characterize acrolein-induced autonomic changes in both normal and TRPA1-knockout mice (KO). Conscious, unrestrained C57BL/6 (WT) and KO mice were exposed to 3 ppm acrolein for 3 h. Separate groups were treated with either atenolol (sympathetic blocker), atropine (parasympathetic blocker) or hexamethonium (autonomic neurotransmission blocker), immediately before exposure. Electrocardiogram (ECG) and heart rate (HR) were recorded continuously before, during and after exposure. Exposure to acrolein produced significant increases in standard deviation of normal-to-normal R-R intervals (SDNN), Root Mean Square of the Successive Differences (RMSSD) and Low-Frequency (LF), as well as an increase in arrhythmia in WT mice. Treatment with atenolol reduced this response while atropine enhanced it, and both drugs blocked the acrolein-induced increase in arrhythmia; hexamethonium had no effect. On the other hand, neither acrolein nor any drug had an effect in the KO mice. Thus, acrolein-induced HRV responses appear to be mediated by a combined parasympathetic and sympathetic modulation. KO mice did not demonstrate any increases in HRV with exposure to acrolein. These data demonstrate that the cardiac effects of irritant air pollutants likely involve disruption of homeostatic balance and altered regulation even in healthy animals.

URLs/Downloads:

Record Details: