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Effects of flavoring compounds used in electronic cigarette refill liquids on endothelial and vascular function

机译:电子香烟综合液对内皮和血管功能的疗效化合物的影响

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Electronic cigarette refill liquids are commercially provided with a wide variety of flavoring agents. A recent study suggested that several common flavors may scavenge nitric oxide (NO) and cause endothelial dysfunction. It was the aim of the present study to investigate the effects of these flavors on NO/cyclic GMP-mediated signaling and vascular relaxation. We tested the flavoring agents for effects on Ca 2+ -induced cGMP accumulation and NO synthase activation in cultured endothelial cells. NO scavenging was studied with NO-activated soluble guanylate cyclase and as NO release from a NO donor, measured with a NO electrode. Blood vessel function was studied with precontracted rat aortic rings in the absence and presence of acetylcholine or a NO donor. Cinnamaldehyde inhibited Ca 2+ -stimulated endothelial cGMP accumulation and NO synthase activation at ≥0.3 mM. Cinnamaldehyde and diacetyl inhibited NO-activated soluble guanylate cyclase with IC 50 values of 0.56 (0.54–0.58) and 0.29 (0.24–0.36) mM, respectively, and caused moderate NO scavenging at 1 mM that was not mediated by superoxide anions. The other compounds did not scavenge NO at 1 mM. None of the flavorings interfered with acetylcholine-induced vascular relaxation, but they caused relaxation of pre-contracted aortas. The most potent compounds were eugenol and cinnamaldehyde with EC 50 values of ~0.5 mM. Since the flavors did not affect endothelium-dependent vascular relaxation, NO scavenging by cinnamaldehyde and diacetyl does not result in impaired blood vessel function. Although not studied in vivo , the low potency of the compounds renders it unlikely that the observed effects are relevant to humans inhaling flavored vapor from electronic cigarettes.
机译:电子卷烟填充液体具有各种调味剂的商业提供。最近的一项研究表明,几种常见的口味可以清除一氧化氮(NO)并导致内皮功能障碍。本研究的目的是研究这些味道对NO /循环GMP介导的信号传导和血管松弛的影响。我们测试了对Ca 2+的影响的调味剂 - 诱导的CGMP积累,培养内皮细胞中没有合成酶活性。没有用无活化的可溶性胍基环化酶研究清除,并且没有用NO电极测量的没有供体释放。在缺乏和存在的乙酰胆碱或不存在的情况下,研究了血管功能。肉桂醛抑制Ca 2+纯化的内皮CGMP积累,没有≥0.3mm的合酶活化。肉桂醛和二乙酰抑制无活化的可溶性胍基酸盐环化酶,分别具有0.56(0.54-0.58)和0.29(0.24-0.36)mm的IC 50值,并使中等不含过滤器未被超氧化物阴离子介导的1mm。其他化合物没有在1毫米处清除不清。没有一种调味剂干扰乙酰胆碱诱导的血管弛豫,但它们引起了预收缩的主动脉的松弛。最有效的化合物是丁烯醇和肉桂醛,EC 50值为〜0.5mm。由于味道不影响内皮依赖性血管弛豫,因此肉桂醛和二乙炔没有清除不会导致血管功能受损。虽然没有在体内研究,但化合物的低效力使得观察到的效果不可能与来自电子烟的人类吸入调味蒸气有关。

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