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

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.

Figure 1. Schematic diagram of the intravital microscopic analysis system (a), and time line of the present experiment (b).

Figure 2. Acute effects of a single dose of flavan-3-ols on several microcirculatory parameters in the cremaster muscle: RBC velocity in the arteriole (a), the number of capillaries recruited (b), and blood flow in the cremasteric artery (c).

Each value represents the mean and standard deviation (n = 8). *p<0.05 and **p<0.01 compared with vehicle-treated control rats.

Figure 3. Acute effects of a single dose of flavan-3-ols on changes of mean blood pressure (a) and heart rate (b) in rats.

Each value represents the mean and standard deviation (n = 8). *p<0.05 and **p<0.01 compared with vehicle-treated control rats.

Figure 4. eNOS phosphorylation and blood nitrate/nitrite levels 60 min after administration of flavan-3-ols.

Each value represents the mean and standard deviation (n = 8). *p<0.05 and **p<0.01 compared with vehicle-treated controls.