Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors.
Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors.
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摄入参与肾上腺素能受体激活的黄烷 3-醇后出现降血压作用。
DOI：
10.1016/j.freeradbiomed.2016.09.008
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Osakabe N.
中科院分区：
文献类型：
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作者：
Saito A;Inagawa K;Ebe R;Fukase S;Horikoshi Y;Shibata M;Osakabe N.
许多流行病学和干预研究都支持摄入富含黄烷3-醇的食物有降压作用。然而，这种作用的机制尚不清楚。我们以前曾报道过哺乳动物服用可可黄烷3-醇组分（FL）后微循环和体循环的变化。我们还证实，在服用FL后，血液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）阻滞剂检查肾上腺素受体是否参与血流动力学改变。首先，我们证实，与给药相比，正常大鼠口服10 mg/kg FL 2周后，平均血压（MBP）显著降低，主动脉内皮一氧化氮合酶（eNOS）水平显著升高。然而，1 mg/kg(-)-表儿茶素（EC）治疗没有观察到这些变化，其中含有几乎等量的10 mg/kg FL。其次，我们观察到单剂量的FL会产生不同的血流动力学变化，例如摄入1 - 100 mg/kg FL后心率（HR）短暂升高，而摄入1 mg/kg EC则不会。此外，尽管在1和10 mg/kg FL后MBP会短暂升高，但在100 mg/kg或1 mg/kg EC时没有观察到这种影响。10 mg/kg FL诱导的HR、MBP和主动脉磷酸化eNOS （p-eNOS）升高可通过AR阻滞剂卡维地洛预处理完全阻止。100 mg/kg FL与α1AR阻滞剂吡唑嗪联合用药可显著降低MBP，提高HR。此外，经β2AR阻断剂butoxamine预处理后，我们观察到100mg /kg FL与α2AR阻断剂育亨宾合用后，血流动力学无明显变化，且100mg /kg FL与α2AR阻断剂育亨宾合用可显著提高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引起的。这种模拟肾上腺素的活动提示了FL的降压作用。
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 10 mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1 mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10 mg/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 1–100 mg/kg FL, but not with 1 mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10 mg/kg FL, this effect was not observed with 100 mg/kg or 1 mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10 mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100 mg/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 100 mg/kg FL. Moreover, the combination of 100 mg/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.