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TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice.

ABSTRACT: 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.

SUBMITTER: Kurhanewicz N

PROVIDER: S-EPMC6220342 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice.

Kurhanewicz Nicole N Ledbetter Allen A Farraj Aimen A Hazari Mehdi M

Toxicology and applied pharmacology 20180405

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 ...[more]

PMID: 29627347

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Project description:Variants in transcription factor 7-like 2 (266096218TCF7L2266096218USuser266096218Gene names have been italicized per house style. Please check and confirm whether there are other instances that need to be italicized or instances where italics have been inappropriately applied.) gene have been found strongly associated with an increased risk of type 2 diabetes, as well as with an impairment of glucagon-like peptide-1 (GLP-1) signalling chain. In rats, stimulation of central GLP-1 receptors increases heart rate and activates autonomic regulatory neurons. We aimed to evaluate the potential role of TCF7L2 gene polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non-related healthy volunteers (mean age 27±3 years). Consistent with previous reports, both single-nucleotide polymorphisms were in strong linkage disequilibrium (D'=0.87, r(2)=0.76). A subset of 167 patients underwent an oral glucose tolerance test while a continuous recording of heart rate variability was performed. At baseline, no differences in fasting plasma insulin, in GLP-1 levels and in LF/HF (low frequency/high frequency) ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INS(AUC) (insulin area under curve), as well as higher LF/HF(AUC) (LF/HF area under curve) values. No difference in GLP-1(AUC) (GLP-1 area under curve) between TCF7L2 gene variants was found. A multivariate analysis including multiple covariates showed that only INS(AUC,) GLP-1(AUC) and TCF7L2 gene variants were independently associated with LF/HF(AUC). In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. Moreover, such effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in increasing cardiovascular risk through enhanced sympathetic nervous system activity.

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TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice.

Publications

TRPA1 mediates the cardiac effects of acrolein through parasympathetic dominance but also sympathetic modulation in mice.

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