Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA; Diabetes and Obesity Center, University of Louisville, Louisville, KY, USA; American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Louisville, KY, USA.
Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA; Diabetes and Obesity Center, University of Louisville, Louisville, KY, USA.
Toxicol Appl Pharmacol. 2021 Sep 1;426:115647. doi: 10.1016/j.taap.2021.115647. Epub 2021 Jul 13.
Acrolein, an electrophilic α,β-unsaturated aldehyde, is present in foods and beverages, and is a product of incomplete combustion, and thus, reaches high ppm levels in tobacco smoke and structural fires. Exposure to acrolein is linked with cardiopulmonary toxicity and cardiovascular disease risk. The hypothesis of this study is the direct effects of acrolein in isolated murine blood vessels (aorta and superior mesenteric artery, SMA) are transient receptor potential ankyrin-1 (TRPA1) dependent. Using isometric myography, isolated aorta and SMA were exposed to increasing levels of acrolein. Acrolein inhibited phenylephrine (PE)-induced contractions (approximately 90%) in aorta and SMA of male and female mice in a concentration-dependent (0.01-100 μM) manner. The major metabolite of acrolein, 3-hydroxypropylmercapturic acid (3HPMA), also relaxed PE-precontracted SMA. As the SMA was 20× more sensitive to acrolein than aorta (SMA EC 0.8 ± 0.2 μM; aorta EC > 29.4 ± 4.4 μM), the mechanisms of acrolein-induced relaxation were studied in SMA. The potency of acrolein-induced relaxation was inhibited significantly by: 1) mechanically-impaired endothelium; 2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); 3) guanylyl cyclase (GC) inhibitor (ODQ); and, 4) a TRPA1 antagonist (A967079). TRPA1 positive immunofluorescence was present in the endothelium. Compared with other known TRPA1 agonists, including allyl isothiocyanate (AITC), cinnamaldehyde, crotonaldehyde, and formaldehyde, acrolein stimulated a more potent TRPA1-dependent relaxation. Acrolein, at high concentration [100 μM], induced tension oscillations (spasms) independent of TRPA1 in precontracted SMA but not in aorta. In conclusion, acrolein is vasorelaxant at low levels (physiological) yet vasotoxic at high levels (toxicological).
丙烯醛是一种亲电的α，β-不饱和醛，存在于食品和饮料中，是不完全燃烧的产物，因此在烟草烟雾和结构火灾中达到高 ppm 水平。丙烯醛的暴露与心肺毒性和心血管疾病风险有关。本研究的假设是丙烯醛在分离的鼠血管（主动脉和肠系膜上动脉，SMA）中的直接作用是瞬时受体电位锚蛋白-1（TRPA1）依赖性的。使用等长肌描记法，将分离的主动脉和 SMA 暴露于逐渐增加的丙烯醛水平下。丙烯醛以浓度依赖性（0.01-100 μM）的方式抑制雄性和雌性小鼠主动脉和 SMA 中苯肾上腺素（PE）诱导的收缩（约 90%）。丙烯醛的主要代谢物 3-羟丙基硫代尿酸（3HPMA）也使 PE 预收缩的 SMA 松弛。由于 SMA 对丙烯醛的敏感性比主动脉高 20 倍（SMA EC 0.8 ± 0.2 μM；主动脉 EC>29.4 ± 4.4 μM），因此研究了丙烯醛诱导松弛的机制。通过以下方法显著抑制丙烯醛诱导的松弛作用：1）机械损伤的内皮；2）Nω-硝基-L-精氨酸甲酯盐酸盐（L-NAME）；3）鸟苷酸环化酶（GC）抑制剂（ODQ）；4）TRPA1 拮抗剂（A967079）。TRPA1 阳性免疫荧光存在于内皮中。与其他已知的 TRPA1 激动剂（包括丙烯基异硫氰酸酯（AITC）、肉桂醛、巴豆醛和甲醛）相比，丙烯醛刺激了更强的 TRPA1 依赖性松弛作用。在预收缩的 SMA 中，但不在主动脉中，高浓度[100 μM]的丙烯醛诱导张力振荡（痉挛），而不依赖于 TRPA1。总之，丙烯醛在低浓度（生理）时具有血管舒张作用，但在高浓度（毒性）时具有血管毒性。
