Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors

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.