Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1.

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ID: 108641
2020
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Abstract
Although crotonaldehyde (CR) is an abundant α,β-unsaturated aldehyde in mainstream cigarette smoke (MCS), the cardiovascular toxicity of inhaled CR is largely unexplored. Thus, male C57BL/6 J mice were exposed acutely (1 h, 6 h, and 4d) and chronically (12 weeks) to CR (at levels relevant to MCS; 1 and 3 ppm), and cardiovascular and systemic outcomes were measured in vivo and in vitro. Diastolic blood pressure was decreased (hypotension) by both acute and chronic CR exposure. Vascular toxicity of inhaled CR was quantified in isolated aorta in response to agonists of contraction (phenylephrine, PE) and relaxation (acetylcholine, ACh; sodium nitroprusside, SNP). Although no change in contractility was observed, ACh-induced relaxations were augmented after both acute and chronic CR exposures whereas SNP-induced relaxation was enhanced only following 3 ppm CR exposure. Because CR is a known agonist of the transient receptor potential ankyrin 1 (TRPA1) channel, male TRPA1-null mice were exposed to air or CR (4d, 1 ppm) and aortic function assessed in vitro. CR exposure had no effect on TRPA1-null aortic function indicating a role of TRPA1 in CR effects in C57BL/6 J mice. Notably, CR exposure (4d, 1 ppm) had no effect on aortic function in female C57BL/6 J mice. This study shows that CR inhalation exposure induces real-time and persistent vascular changes that promote hypotension-a known risk factor for stroke. Because of continued widespread exposures of humans to combustion-derived CR (environmental and tobacco products), CR may be an important cardiovascular disease risk factor.
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lynch2020acutetoxicology Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Lynch, Jordan;Jin, Lexiao;Richardson, Andre;Jagatheesan, Ganapathy;Lorkiewicz, Pawel;Xie, Zhengzhi;Theis, Whitney S;Shirk, Gregg;Malovichko, Marina;Bhatnagar, Aruni;Srivastava, Sanjay;Conklin, Daniel J;
Journal toxicology and applied pharmacology
Year 2020
DOI
S0041-008X(20)30246-5
URL
Keywords
blood pressure endothelial dysfunction cigarettes tobacco products aldehydes transient receptor potential ankyrin-1

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