Flow mediated dilatation

Ellis et al. [72] recently studied the effects of short- and long-term vitamin C therapy in the patients with chronic heart failure (CHF). It was found that oxygen radical production and TBAR product formation were higher in patients with CHF than in control subjects. Both short-term (intravenous) and long-term (oral) vitamin C therapy exhibited favorable effects on the parameters of oxidative stress in patients the treatments decreased oxygen radical formation and the level of lipid peroxidation and improved flow-mediated dilation in brachial artery. However, there was no correlation between changes in endothelial function and oxidative stress. 

The effects of raloxifene on the vascular endothelium have been studied in 19 subjects who underwent endothelial function testing at baseline and after treatment with placebo or raloxifene (60 mg/day for 6 weeks) (27). The findings in this small short-term study were entirely positive. Brachial artery diameter change (flow-mediated dilatation) increased 5.0% with placebo and 8.6% with raloxifene in response to a hyperemic stimulus. The ratio of AUC response to AUC reference with the use of laser Doppler measures was 1.18 for placebo and 1.28 for raloxifene. Flow-mediated dilatation and AUC ratio correlated significantly. The authors concluded that raloxifene enhanced endothelial-mediated dilatation in brachial arteries and digital vessels in these women, and they discussed the drug s possible cardioprotective effect. 

The literature on vascular responses to dietary components [e.g., Fitzpatrick et al., 1995] has increased substantially in recent years. Short-term and long-term consumption of black tea was shown to reverse endothelial dysfunction in patients with coronary artery disease [Duffy et al., 2001]. On the acute shortterm time frame, which is taken here as the responses observed between 0 and 6 h, we demonstrated increases in flow-mediated dilation of the brachial artery upon intake of high-flavanol cocoa drink, but not of low-flavanol cocoa drink, in a crossover study [Heiss et al., 2003]. The effect of the flavanol-rich cocoa drink on flow-mediated dilation as well as the increase in circulating... 

As in the studies on tea [Duffy et al., 2001], a chronic longer-term vascular response was identified with high-flavanol cocoa, when the flavanol-containing beverage was administered repetitively over several days [Heiss et al., 2007], This effect was clinically characterized as continuously elevated baseline of flow-mediated dilation, on top of which the short-term effect was added on with every new dose this additive effect was at about the same magnitude as without the pretreatment. 

Heiss C, Finis D, Kleinbongard P, Hoffmann A, Rassaf T, Kelm M, Sies H. 2007. Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week. J Cardiovasc Pharmacol 49 74-80. 

Approximately half of randomized clinical trials demonstrated a beneficial effect of soy supplementation on endothelial function, shown either by increased brachial artery diameter or flow-mediated dilation, or decreased peak flow velocity. Of the studies reporting a positive effect, four reported an improvement in endothelial function after 4-6 weeks of supplementation with 20—25 g/d soy protein (Cuevas et al., 2003 Cupisti et al., 2007 Steinberg et al., 2003 Yildirir et al., 2001). The study populations in these four studies consisted of renal transplant patients and postmenopausal women. Three studies ranging from 6 weeks to 1 year also demonstrated an improvement in endothelial function in postmenopausal women following daily supplementation with soy isoflavones (54—90 mg/d) (Colacurci et al., 2005 Lissin et al., 2004 Squadrito et al., 2003). In addition, Azadbakht et al. (2007a) reported a decrease in E-selectin, a biomarker of endothelial function, after 8 weeks of soy-nut consumption in postmenopausal women. However, insufficient evidence is available to determine differential effects of soy protein dose or type of soy products on changes in endothelial function (Balk et al., 2005). 

Fenofibrate (propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate), a fibric acid derivative (Fig. 7.6), mainly exerts its effect via the activation of speciflc nuclear receptor called peroxisome proliferator-activated receptor alpha (PPARa). This PPARa agonist is primarily used to decrease the cholesterol levels in cardiovascular diseases patients. Like statins, fenofibrate also reduces triglycerides and low- and very low density protein levels. It also increases high-density lipoprotein levels in the body. Fenofibrate also has nonlipid (i.e., pleiotropic) effects (reduction in fibrinogen, C-reactive protein, and uric acid levels and improvement in the flow-mediated dilatation). 

Fig. 8. Impairment in endothelial function after a high fat meal in normocholesterolemic coronary artery disease (CAD) patients and control subjects [data from Zhao etal. (89), reproduced with permission]. Flow-mediated vasodilation of the brachial artery was evaluated by high-resolution ultrasound before and after a single high-fat meal (800 kcal 50 g fat). Impairment of flow-mediated dilation was more severe in CAD patients (44.4%) than in control patients (26.0%).

In vivo vasodilation Two methods observe the release of NO by the endothelium by measuring changes in blood flow in humans. In flow-mediated dilatation, the diameter of the brachial artery is measured with ultrasound. The vasodilation is induced by the increase of arterial shear stress after the release of an inflatable cuff around the arm. Plethysmography measures the blood flow via the volume changes of the forearm after venous occlusion. Quantification of NO is not possible in either method and the diagnostic value is limited as individuals show considerable variations in systemic response. 

The mechanisms which are causing the biological effects of flavanols include the modulation of cell signaling pathways [95] and the regulation of nitric oxide (NO) homeostasis, which in turn influences the flow-mediated dilation in capillaries. The antioxidative potential of the flavanols leads to scavenging free radicals and inhibits lipid peroxidation [96]. 

Several epidemiological studies have linked a protective effect against cardiovascular diseases and regular consumption of either red wine [7, 8, 98] or polyphenol-rich sources such as green tea [14,15,99], cocoa, or chocolate [16,17]. Since many cardiovascular diseases are associated with an impaired endothelial function, the evaluation of the endothelial function is of great importance. In humans, the endothelial function is often assessed by the flow-mediated dilatation (FMD). For this purpose, reactive hyperemia is induced after a transient ischemia in the upper arm using an inflatable cuff like that used for the measurement of blood pressure, while the diameter of the brachial artery is monitored continuously at the elbow level by ultrasound. The cuff is inflated tmtil the occlusion of the brachial artery, which is maintained for 5 min before the blood flow is released. The reperfusion then induces an endothelium-dependent dilatation of the brachial artery due to the increased shear stress, the most important physiological activator of eNOS. Impaired endothelial function, assessed by FMD, has been reported as an independent predictor of cardiovascular outcome in subjects with cardiovascular risk factors or established cardiovascular diseases [18]. 

Yeboah J, Crouse JR, Hsu PC, Burke GL, Herrington DM (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults the Cardiovascular Health Study. Circulation 115(18) 2390-2397... 

Moreover, numerous studies have been developed on CHD patients. The intake of red grape polyphenol extract - which contains epicatechin, catechin, gallic acid, trans-resveratrol, s-viniferin, rutin, quercetin, p-coumaric, and ferulic acid -improved the endotheUal function in CHD patients. Similar results have been foimd for red grape juice [123]. Hypercholesterolemic patients were asked to consume red grape juice (500 mL/day) and red wine (250 mL/day) for 14 days. Results showed increased brachial artery flow-mediated dilation in both cases. However, increased endothelium-independent vasodilation was observed only in red wine-drinking patients [124]. Similar results and the same conclusions were drawn from a similar study on red grape juice. The daily ingestion of moderate... 

Another important aspect of the mechanism of tea in controlling cardiovascular diseases is the positive effects on endothelial functions. Abnormalities in endothelial function lead to several disorders, including CVDs. The daily consumption of black tea (900 ml/day) for 4 weeks improved the endothelium-dependent flow-mediated dilation of the branchial artery associated with coronary artery disease [100]. Similar effects on branchial artery dilation have been reported with green tea... 

Cardiovascular In a study in 23 subjects initiating ARVs, a significantly lower flow mediated dilatation (FMD, a marker of endothelial function) of the brachial artery was noted with EFV as compared to Pl-based regimens at 12months [216 j. Use of FTC/TDF/EFV was associated with a reduction in FMD at 6 and 12months compared to those not on this combination. The authors suggest this may play a role in cardiovascular risk. 

---