Chronic ethanol consumption enhances inducible endothelium-dependent hyperpolarizing factor-mediated relaxation in the rat artery
Chronic ethanol consumption enhances inducible endothelium-dependent hyperpolarizing factor-mediated relaxation in the rat artery
复制标题
慢性乙醇消耗增强大鼠动脉中诱导性内皮依赖性超极化因子介导的舒张
DOI：
10.1016/j.ejphar.2019.172759
复制
发表时间：
2019
影响因子：
5
通讯作者：
Hatake Katsuhiko
中科院分区：
文献类型：
--
作者：
Yuui Katsuya;Kudo Risa;Kasuda Shogo;Hatake Katsuhiko
可诱导的内皮依赖性超极化因子(IEDHF)通路被激活，作为对身体不利变化的代偿反应。它使血管松弛，并维持器官内循环的动态平衡。少量到中等剂量的乙醇可增强血管松弛。然而，其机制和iEDHF通路在这一过程中的参与尚不清楚。因此，我们研究了iEDHF介导的、乙酰胆碱诱导的、内皮依赖性的血管内皮依赖性松弛。给予标准饲料(S对照组)、利伯氏对照组(L对照组)和利伯氏乙醇饲料(乙醇组)。SMA松弛通过等长张力测量进行评估。免疫印迹法检测花生四烯酸15脂氧合酶(ALOX15)和可溶性环氧化物水解酶(SEH)。乙酰胆碱诱导的内皮依赖性松弛在无水乙醇组显著大于对照组。这些差异在PGI2后持续存在，并且没有被阻断。因此，乙酰胆碱引起的松弛增加是由EDHF介导的。然而，在Etoh组，它被iEDHF抑制剂阻止。乙醇组ALOX15和sEH蛋白表达水平均高于L对照组。慢性酒精摄入增加乙酰胆碱引起的松弛是通过iEDHF途径实现的。这一机制可能对乙醇引起的血压升高起到补偿作用。这项研究表明，iEDHF是在适当的饮酒过程中诱导的，可能有助于预防心血管疾病的发生。
The inducible endothelium-dependent hyperpolarizing factor (iEDHF) pathway is activated as a compensatory response to adverse changes in the body. It causes vasorelaxation and maintains circulatory homeostasis in the organs. Small to moderate quantities of ethanol enhance vascular relaxation. However, its mechanism and the involvement of the iEDHF pathway in this process are unknown. Therefore, we studied iEDHF-mediated, acetylcholine-induced, endothelium-dependent relaxation in the superior mesenteric arteries (SMAs) of rats chronically fed ethanol. Rats were administered a standard diet (S-Control group), Lieber's control diet (L-Control group), or Lieber's ethanol diet (EtOH group). SMA relaxation was assessed by isometric tension measurements. Arachidonate 15-lipoxygenase (ALOX15) and soluble epoxide hydrolase (sEH) were determined by immunoblot. Acetylcholine-induced, endothelium-dependent relaxation was significantly greater in the EtOH than the control groups. These differences persisted after PGI2 and NO blockade. Thus, the increase in acetylcholine-induced relaxation was EDHF-mediated. In the EtOH group, however, it was prevented by iEDHF inhibitors. ALOX15 and sEH protein expression levels were higher in the EtOH than the L-Control group. The increase in acetylcholine-induced relaxation by chronic ethanol consumption was mediated by the iEDHF pathway. This mechanism may compensate for the blood pressure elevation induced by ethanol. This study suggests that iEDHF is induced during proper drinking and may help prevent the onset of cardiovascular conditions.