Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

Kodai Ingawa,Naomi Osakabe,Yusuke Matsumura,Masahiro Shibata,Nozomi Aruga

doi:10.1371/journal.pone.0094853

Abstract

Several systematic reviews have reported that flow mediated dilatation (FMD) was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

Highlights

Cocoa bean, the seed of Theobroma cocoa, is one of the ingredients in chocolate and cocoa
The marked elevation of Red blood cell (RBC) velocity in the arterioles can be seen in the video image, and this confirms that endothelial cells were exposed to severe shear stress
The average RBC velocity in the arterioles shortly after treatment with flavan-3-ols is shown in Fig.2 (a), and a significant difference was observed compared with vehicle from 5 min after treatment until the end of the observation period

Summary

Introduction

The seed of Theobroma cocoa, is one of the ingredients in chocolate and cocoa. Recent epidemiological meta-analyses have suggested that ingestion of chocolate reduces the risk of cardiovascular disease and stroke [4,5]. Numerous studies support the idea that flavan-3ols in cocoa reduce the risk of cardiovascular disease by improving hypertension, dyslipidemia and glucose intolerance [6,7,8,9,10,11,12]. Flow-meditated dilation (FMD), which is a non-invasive method to assess endothelial function, was shown to be significantly increased shortly after ingestion of dark chocolate in healthy or mild hypertensive subjects [13,14,15]. It is well known that endothelial function is affected by cardiovascular risk factors, and can be influenced by exercise [16,17] or behavioral factors [18]. It was reported that the blood NO metabolite level was increased after ingestion of chocolate; there is little information about the mechanisms responsible for this effect

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Discussion

Conclusion