Institute of Environmental Medicine and Toxicology, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China.
Institute of NBC Defence, Beijing, 102205, China.
Chem Biol Interact. 2019 Aug 25;309:108710. doi: 10.1016/j.cbi.2019.06.023. Epub 2019 Jun 11.
Formic acid is a common organic acid used in many industrial processes. There is a paucity of research on the direct toxicity of formic acid and how it might affect the cardiovascular system. This study aimed to understand the effect of formic acid on vascular tension in an animal model and the underlying mechanism. Results found that the vasodilation induced by formic acid was related to the endothelium. When the dosage of formic acid was 1 mM or 5 mM, the vasodilation of endothelium-intact rings was partially suppressed by l-NAME, NS-2028 and nifedipine, and vasoconstriction caused by CaCl was inhibited, and the mRNA levels of eNOS, the activity of NOS (tNOS, iNOS and cNOS) and the level of NO and cGMP were significantly increased. Results also found that eNOS protein expression was significantly enhanced by 5 mM of formic acid. These results suggest formic acid can relax the aortic vessels of rats in a dose-dependent pattern. Further, the mechanism of the formic acid-induced vasodilatation likely involved the NO/cGMP pathway. Finally, the current study has revealed that vasodilation induced by high concentrations of formaldehyde may be the effect of the metabolite formic acid. This study will help further inform the etiologies of formic acid-related angiocardiopathies.
甲酸是一种在许多工业过程中使用的常见有机酸。关于甲酸的直接毒性以及它如何影响心血管系统的研究很少。本研究旨在了解甲酸在动物模型中对血管张力的影响及其潜在机制。结果发现,甲酸诱导的血管舒张与内皮有关。当甲酸剂量为 1mM 或 5mM 时,内皮完整环的血管舒张部分被 l-NAME、NS-2028 和硝苯地平抑制,氯化钙引起的血管收缩被抑制,eNOS 的 mRNA 水平、NOS(tNOS、iNOS 和 cNOS)的活性以及 NO 和 cGMP 的水平均显著升高。结果还发现,5mM 的甲酸可显著增强 eNOS 蛋白表达。这些结果表明,甲酸可呈剂量依赖性方式使大鼠主动脉血管舒张。此外,甲酸诱导的血管舒张的机制可能涉及 NO/cGMP 途径。最后,本研究揭示了高浓度甲醛引起的血管舒张可能是其代谢产物甲酸的作用。本研究将有助于进一步阐明与甲酸相关的血管心脏病的病因。