Saito Akiko, Inagawa Kodai, Ebe Rikihiko, Fukase Shinobu, Horikoshi Yukari, Shibata Masahiro, Osakabe Naomi
Department of Bio-science and Engineering, Shibaura Institute of Technology, Saitama, Saitama, Japan.
Department of Bio-science and Engineering, Shibaura Institute of Technology, Saitama, Saitama, Japan.
Free Radic Biol Med. 2016 Oct;99:584-592. doi: 10.1016/j.freeradbiomed.2016.09.008. Epub 2016 Sep 9.
A lot of epidemiological and intervention studies support the hypotensive action resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms of this action remain unclear. We have reported previously on the alteration of the micro- and systemic circulations after administration of a flavan 3-ol fraction (FL) derived from cocoa in mammals. We also confirmed that blood catecholamine levels increase significantly after administration of FL. In the present study, we examined whether adrenaline receptors are involved in the hemodynamic changes using several adrenaline receptor (AR) blockers. First, we confirmed that mean blood pressure (MBP) decreased significantly and aortic endothelial nitric oxide synthase (eNOS) levels increased significantly following oral treatment of 10mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10mg/kg FL. Secondly, we observed that a single dose of FL produced different hemodynamic changes, such as a transient elevation in heart rate (HR) after ingestion of 1-100mg/kg FL, but not with 1mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10mg/kg FL, this effect was not observed with 100mg/kg or 1mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100mg/kg FL and an α1AR blocker, prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In addition, after pretreatment with the β2AR blocker, butoxamine, we observed no significant hemodynamic changes with or without 100mg/kg FL. Moreover, the combination of 100mg/kg FL and the α2AR blocker, yohimbine, markedly increased MBP, HR and aortic p-eNOS level. These results suggested that the postprandial hemodynamic changes after a single oral dose of FL were induced by an adrenergic effect. This adrenomimetic activity suggested the involvement of a hypotensive effect of FL.
许多流行病学和干预研究都支持摄入富含黄烷 - 3 - 醇的食物会产生降压作用。然而，这种作用的机制仍不清楚。我们之前曾报道过给哺乳动物施用源自可可的黄烷 - 3 - 醇组分（FL）后微循环和体循环的改变。我们还证实，施用FL后血中儿茶酚胺水平显著升高。在本研究中，我们使用几种肾上腺素受体（AR）阻滞剂检查了肾上腺素受体是否参与血流动力学变化。首先，我们证实，与给予赋形剂相比，正常大鼠口服10mg/kg FL 2周后平均血压（MBP）显著降低，主动脉内皮型一氧化氮合酶（eNOS）水平显著升高。然而，用1mg/kg（ - ） - 表儿茶素（EC）治疗时未观察到这些变化，1mg/kg EC含有的量与10mg/kg FL几乎相当。其次，我们观察到单次给予FL会产生不同的血流动力学变化，例如摄入1 - 100mg/kg FL后心率（HR）短暂升高，但1mg/kg EC不会。此外，虽然1mg/kg和10mg/kg FL给药后MBP短暂升高，但100mg/kg或1mg/kg EC未观察到这种效应。10mg/kg FL诱导的HR、MBP和主动脉磷酸化eNOS（p - eNOS）的升高被AR阻滞剂卡维地洛预处理完全阻断。100mg/kg FL与α1AR阻滞剂哌唑嗪联合治疗可显著降低MBP，而HR升高增强。此外，用β2AR阻滞剂布托沙明预处理后，无论是否给予100mg/kg FL，我们均未观察到显著的血流动力学变化。此外，100mg/kg FL与α2AR阻滞剂育亨宾联合使用可显著提高MBP、HR和主动脉p - eNOS水平。这些结果表明，单次口服FL后的餐后血流动力学变化是由肾上腺素能效应诱导的。这种拟肾上腺素活性提示FL具有降压作用。
