Acute responses of regional vascular conductance to oral ingestion of fructose in healthy young humans
© Endo et al.; licensee BioMed Central Ltd. 2014
Received: 3 February 2014
Accepted: 1 May 2014
Published: 17 May 2014
Recently, it was reported in healthy young subjects that fructose containing drinks increased blood pressure acutely, without any apparent change in total vascular conductance (TVC). However, because it is well known that the splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be the concomitant vasoconstriction in other peripheral region(s) that is responsible for this finding. Thus, the purpose of this study was to determine the acute response of regional VC to oral fructose ingestion in young healthy humans.
In 12 healthy young subjects, mean arterial blood pressure (MAP), heart rate, cardiac output, and blood flow (BF) in the superior mesenteric (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin BF, were measured continuously for 2 h after ingestion of 400 ml fructose solution (containing 50 g fructose). Regional VC was calculated as BF/MAP. MAP increased for 120 min after fructose ingestion without any change in TVC. While VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin decreased.
While TVC was apparently unchanged during the 2 h after fructose ingestion, there were coincident changes in regional VCs in the peripheral circulation, but no net change in TVC.
Keywordsfructose blood pressure vascular conductance central circulation peripheral circulation
In recent decades, daily consumption of dietary fructose has increased gradually. In addition to fruit, carbonated beverages containing a form of high-fructose corn syrup have been implicated in the increase . Long-term consumption of fructose results in an increase in plasma triglycerides in humans and animals [2–6], and is considered a significant dietary problem in advanced countries associated with obesity and arteriosclerosis [7–9]. Several recent studies have suggested that dietary fructose consumption may lead to the development of cardiovascular diseases such as hypertension [5, 8, 10, 11]. The current understanding to the background of fructose-derived hypertension is unclear as to whether overconsumption of fructose itself induced the elevation of BP directly or indirectly (via hyperuricemia, which is subsequently followed by activation of the rennin-angiotensin-aldosterone system and damage to the renal tubule [11, 12]).
The blood pressure (BP) was greater after consumption of a high fructose diet for eight weeks compared with rats consuming a normal diet in rats . In older people, the BP acutely increased following ingestion of fructose-containing drinks . Even in healthy young subjects, Brown et al.  showed that oral consumption of a 50-g pure fructose-containing drink rapidly increased BP, which was sustained for at least a few hours, whereas there was no comparable effect after consumption of either a glucose-containing drink or water . They suggested that fructose-specific acute elevations in BP were mainly mediated not by a decreased peripheral vascular response (that is, no change in total vascular conductance, TVC), but by a sustained elevation of cardiac output (CO). However, it is well known that fructose ingestion results in a slight, but significant, increase in acute splanchnic circulation . Together with these results, it is hypothesized that regional VC in areas such as the viscera, limbs, and/or skin would be acutely changed, even while TVC remains apparently unchanged. Therefore, we did this study as a pilot to reconfirm the results by Brown et al. , including the simultaneous measurements of peripheral VCs in several targeted arteries with our technique (that is, pulsed Doppler ultrasound sonography).
Based on the findings above, focusing on regional VC after fructose ingestion is important because the accumulation of acute effect(s) to regional cardiovascular regulation may be a precursor to a more chronic phenomenon, that is, fructose-induced hypertension. Thus, the purpose of this study was to determine acute responses of regional VC to oral fructose ingestion in young healthy humans.
Twelve healthy young subjects (four males, eight females) were studied. The mean (± SEM) age, height, and body mass of the subjects was 21.5 ± 1.4 years, 160.0 ± 6.4 cm, and 50.8 ± 4.3 kg, respectively. All subjects were informed of the purpose, protocol, and risks associated with the procedures before giving written informed consent to participate in the study, which was approved by the local Ethics Committee of Hiroshima and was conducted in accordance with the Declaration of Helsinki. The menstrual cycle in the female subjects was not controlled.
The subjects arrived at the laboratory in the morning after a 12-hour fast. After baseline measurements for 30 min, the subjects ingested a 400-ml fructose solution. Then, the subjects rested for 120 min in a supine position, except at the time of drink ingestion. The subjects consumed the drink within 3 min in a sitting position. The test drink was a water-based solution containing 50 g fructose. Unsweetened lemon juice (10 ml) was added to the drink to provide a more appetizing taste for the participants. The ambient temperature of the experimental room was kept at 23 ± 0.5 °C and 40-50% relative humidity by a thermal feedback device.
The BF of skin in the right forearm was measured continuously using a laser rheometer (ALF21; Advance, Tokyo, Japan).
All data are expressed as mean ± SEM. The effect of time on the variables was examined using repeated measures one-way analysis of variance (ANOVA). When significant differences were detected, Dunnett’s post-hoc test was used to reveal the effect of time against the baseline (that is, values before ingestion). The level of statistical significance was set at P <0.05. All analyses were performed using SPSS 12.0 for Windows (SPSS, Chicago, IL, USA).
Results and discussion
The purpose of this study was to determine acute responses of regional VC to oral fructose ingestion in young healthy humans. As expected from a previous study , oral fructose ingestion initiated an acute and significant elevation of MAP lasting for at least two hours. This was partially induced by a change not in TVC, but increased CO via a sustained elevation in HR. While TVC was apparently unchanged during the two hours after ingestion, there were changes in regional VC, but no net change in TVC.
The increase in BP associated with oral fructose ingestion was characterized by gradual increases in CO and HR, but no compensatory reduction in TVC (Figure 1). The acute BP elevation was partially induced by an elevation in CO via a concomitant increase in HR. This result is in agreement with previous studies [7, 18]. Indirect measures using HR variability have indicated parasympathetic withdrawal and sympathetic activation compared with baseline . Vollenweider et al.  showed no change in muscle sympathetic nervous activity in the lower limbs during continuous venous infusion of fructose for two hours. The increased HR in this study seemed to be induced by the parasympathetic withdraw, while the mechanism of the cardiac autonomic stimulation following ingestion of fructose remains to be established.The novel finding in the present study was that over the 120 min after fructose drink ingestion, the BP showed the acute elevation. During such duration, while the TVC was unchanged, the regional VCs in several peripheral vasculatures showed different features of changes (Figure 2). In detail, during the first 60 min after oral fructose ingestion, VC in the SMA (supply routes to the duodenum, small intestine, ascending colon, transverse colon, and pancreas) rapidly increased, whereas VC in the BA and PA (supply to mainly skeletal muscles and skin) was reduced. During the subsequent hour (that is, 60 to 120 min), VC in the SMA had already returned to baseline, whereas VC in the RA gradually decreased. In addition, VC in the BA, PA, and forearm skin gradually returned to baseline (that is, the changes in VC among the BA, PA, and forearm skin were very similar).
These results indicate that, after oral fructose ingestion, the vascular beds in peripheral limbs (that is, arms and presumably lower limbs) were vasoconstricted to compensate for vasodilation in the splanchnic region (that is, SMA) for the digestion and absorption of fructose. Such peripheral vasoconstriction seems to be derived from systemic sympathetic activation, since Jansen et al.  demonstrated acute increased serum norepinephrine levels during one hour after oral fructose ingestion.
We observed systemic and peripheral circulatory responses to oral fructose ingestion over a 2-hour period. Fructose ingestion was associated with an acute elevation in BP, which was associated with an increase in CO. Although fructose ingestion did not change TVC, there were several different changes in regional vascular responses over the period, which may, with repeated exposure, increase the risk of hypertension-induced arteriosclerosis and events such as stroke and cardiovascular disease in addition to hyperlipidemia.
mean arterial blood pressure
superior mesenteric artery
total vascular conductance
This study was supported in part by JSPS KAKENHI (#24700701 to Endo, #22370091 to Fukuoka and #23650390 to Fukuba) and the Descente and Ishimoto Memorial Foundation for the Promotion of Sports Science.
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