Acute Flavanol Supplementation Improves the Attenuated Cerebral Vasodilatory Capacity in Young African Americans

African Americans (AA) have increased risk for cerebral vascular disease including stroke, Alzheimer’s disease, or dementia relative to Caucasian Americans (CA). Our recent study found that AA have attenuated cerebral vasodilatory response to rebreathing-induced hypercapnia when compared with CA. Thus, we hypothesized that acute flavanol intake restores blunted cerebral responses in AA. Fourteen healthy college-aged AA and 14 age- and sex-matched CA participants were studied. A four-parameter logistic regression was used for curve fitting the responses of cerebral vascular conductance (%CVCi) relative to changes in end-tidal carbon dioxide concentration. In AA, there were significant improvements in total range of changes in %CVCi (a) and the maximum increase in %CVCi (y0) with flavanol beverage (a; pre: 46.4 ± 16 vs. post: 64.4 ± 19 %CVCi; P = 0.007, y0; pre: 151.1 ± 18 vs. post: 166.0 ± 22 %CVCi; P = 0.002); however, there were no differences in a and y0 with placebo (a; pre: 52.5 ± 19 vs. post: 51.7 ± 17 %CVCi; P = 0.35, y0; pre: 156.2 ± 20 vs. post: 151.3 ± 17 %CVCi; P = 0.26). In CA, no differences in a and y0 with flavanol (a; pre: 73.7 ± 18 vs. post: 71.7 ± 22 %CVCi; P = 0.70, y0; pre: 175.7 ± 20 %CVCi vs. post: 175.6 ± 22 %CVCi; P = 0.99) or placebo (a; pre: 75.7 ± 15 vs. post: 80.1 ± 20 %CVCi; P = 0.24, y0; pre: 177.4 ± 21 %CVCi vs. post: 180.6 ± 25 %CVCi; P = 0.45) were observed. In conclusion, acute flavanol supplementation increases the total range of changes in cerebral vascular conductance as well as maximum vascular conductance in AA, effectively abolishing the ethnic-related difference in cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia

The Effect of a High Fat Meal on Cerebral Vascular Function

It is well known that a single high fat meal (HFM) causes a robust and transient elevation in serum triglycerides (TG). This elevation in serum TG is a primary contributor to the post-prandial attenuation of peripheral vascular endothelial function, as assessed by flow-mediated dilation in the brachial artery. Whether a similar impairment in vascular reactivity can be observed in the cerebral circulation remains unknown, and was the focus of this investigation. PURPOSE: To test the hypothesis that cerebral vascular function is impaired following a HFM. METHODS: End-tidal carbon dioxide partial pressure (PETCO2), middle cerebral artery blood velocity (MCAVmean), calculated cerebral vascular conductance index (CVCI; MCAVmean/mean arterial pressure) and cerebral vasodilator response to rebreathing induced hypercapnia (% increase in CVC from baseline at common maximal ΔPETCO2) were assessed in 6 healthy young men (27 ±5 years). Measures were assessed during fasted baseline and again at 2 and 4 h post meal consumption (HFM day) or at a similar time point in the fasted state (TC day). The two visits were separated by 2-7 days and were conducted in a randomized order. Blood lipids were assessed at baseline and at the 2 h time point into each respective condition. RESULTS: As expected, consumption of the HFM significantly elevated serum TG concentrations relative to TC at 2 h (HFM: 101±38 to 169±77mg/dl, TC: 107±32 to 92±31mg/dl, P=0.007). However, the HFM had no effect of cerebral vasodilator capacity during rebreathing induced hypercapnia. The maximal increase in %CVC achieved at the highest common ΔPETCO2 during all conditions within each subject was unchanged during 2hr and 4hr post HFM or TC (condition x time interaction: P=0.96). Similarly, the slope of the change in %CVC per change in ΔPETCO2 was unaffected by HFM across time (P=0.49). CONCLUSION: Contrary to our hypothesis, and unlike the peripheral vasculature, our preliminary data suggest that the cerebral circulation appears to be protected from the acute negative effects of a high fat meal

Cutaneous microvascular endothelium dependent vasodilation is impaired in young obese subjects

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Effect of Acute Antioxidant Consumption on Cardiac Baroreflex Sensitivity in Young Healthy Adults

There is an emerging body of evidence in animals indicating that elevated oxidative stress impairs baroreflex sensitivity (BRS) function, however studies in healthy humans have yielded equivocal results. One potential reason for this discrepancy is that previous studies have used individual antioxidant treatments (e.g., Vitamin C only) to investigate the effect of oxidative stress on BRS. Recent studies in healthy humans have demonstrated significant reductions in reactive oxygen species using an antioxidant cocktail (AOC; Vitamin C, Vitamin E, and Co-enzyme Q10) suggesting the effectiveness of this treatment. Whether this AOC induced reduction in oxidative species affects BRS in young, healthy adults remains unknown. PURPOSE: We tested the hypothesis that AOC will improve cardiac BRS in young healthy adults. METHODS: Five young men were studied on two separate days: placebo (sugar pills) and AOC (2000 mg Vitamin C, 150 IU Vitamin E and 100 mg Co-enzyme Q10) performed in random order. Resting heart rate (ECG) and arterial blood pressure (automated sphygmomanometer and finger photoplethysmography) were measured 90 minutes after AOC or placebo (a time period this AOC has been shown to have peak effects on oxidative stress). Spontaneous cardiac BRS was determined for all sequences combined (overall BRS), and also separately for up (increase systolic blood pressure: increase R-R interval) and down (decrease systolic blood pressure: decrease R-R interval) sequences. RESULTS: Systolic blood pressure on AOC day tended to be lower relative to the placebo day (127 ± 4 vs. 131 ± 5; p=0.098). However, no differences in overall cardiac BRS were found between placebo and AOC (18.0 ± 2.7 vs.17.3 ± 2.6 ms/mmHg; p=0.59). Likewise, up sequences (17.02 ± 2.9 vs 14.04 ± 4.0 ms/mmHg; p=0.51) and down sequences (18.0 ± 2.7 placebo vs. 18.0 ± 2.6 ms/mmHg AOC; p=0.98) were not different between conditions. Equal number of sequences were found between the placebo and AOC days. CONCLUSION: These preliminary data suggest that antioxidant treatment does not affect resting cardiac BRS in young, healthy men

Racial Differences in Vascular Function in Response to Mental Stress

African Americans (AA) have a higher prevalence of hypertension and other cardiovascular (CV) complications compared to other populations. While the reasons for this elevated CV disease risk are multifactorial, vascular dysfunction is a key contributing factor. It has been previously shown that mental stress, induced by mental arithmetic, results in a significant increase in forearm blood flow (FBF). This response has been predominantly attributed to the release and vasodilatory effect of Nitric Oxide (NO). In this regard, a previous study has reported that AA have an attenuated increase in FBF as compared to Caucasians (CA) in response to mental stress, which may be related to impaired vascular function and thus elevated CV disease risk in AA. However, this study was conducted in a middle-age cohort (mid to late 40’s). Whether this attenuation is present in a young relatively healthy population is unknown. PURPOSE: The purpose of this study was to test the hypothesis that the vasodilatory response to mental stress is blunted in a relatively young and healthy AA population. METHODS: 6 relatively healthy young AA and 6 CA males (AA age: 22 + 2.6, CA age: 23 + 4.6) participated in this study. All measurements were obtained in the morning following an overnight fast. Brachial artery diameter and blood velocity were assessed using high resolution duplex ultrasound. Mental stress was induced by asking subjects to subtract 7 continuously from a 3-digit number while attempting to report answers at a pace set by a 60 bpm metronome. The 3-digit number was changed at 20 second intervals. FBF was measured during a two minute baseline followed by 3 minutes of mental stress. Vascular function was assessed as the absolute peak blood flow response (ml/min) as well as peak conductance (ml/min/mmHg) during the mental stress. RESULTS: The absolute peak flow (AA: 183 + 39 ml/min, CA: 307 + 127 ml/min; P = 0.05) were significantly greater in CA compared to AA. The maximum increase in conductance (AA: 2.03 + 0.32 ml/min/mmHg, CA: 3.69 + 1.39 ml/min/mmHg; P = .02) was also significantly higher in CA as compared to AA. CONCLUSION: This preliminary data supports our hypothesis that vascular function in response to mental stress is attenuated in young healthy AA as compared to their CA counterparts

Impaired Muscarinic Receptor-Mediated Vasodilation in Young, Black Men is Not Influenced by Oxidative Stress

The black population (BL) presents an elevated risk for hypertension and cardiovascular disease relative to other populations. While the cause is multifactorial, vascular dysfunction is indicated as a key contributing factor. Young BL men exhibit microvascular dysfunction across a variety of stimuli including local heating and muscarinic receptor-mediated dilation (MRMD) of the cutaneous circulation. Previously, our group has noted that increased NADPH oxidase (NOX) and xanthine oxidase (XO)-derived oxidative stress impairs local heating-mediated dilation in BL men. However, whether oxidative stress from these sources or from uncoupled endothelial nitric oxide synthase (eNOS) contributes to blunted MRMD in BL men is currently unknown. PURPOSE: The present study aimed to test the hypothesis that blunted MRMD in BL men will be ameliorated following inhibition of oxidative stress from NOX, XO, or uncoupled eNOS via apocynin, allopurinol, and tetrahydrobiopterin (BH4; an essential eNOS cofactor), respectively. METHODS: To test this hypothesis, four intradermal microdialysis membranes were placed in the dorsal forearm of 11 BL men (mean±SD; age: 23±4 y) and red blood cell flux (RBF) responses to 100µM methacholine (MCh) infusions were observed. This dose has been shown in preliminary testing to elicit approximately a 50% blunted increase in cutaneous vascular conductance (CVC) in BL compared to whites. Following trauma resolution, each site received one of four infusions for 30-min: lactated Ringer’s, 100µM apocynin, 10µM allopurinol, or 10mM BH4. Each site was then locally heated to 33°C for 10-min to establish baseline RBF. MCh (MCh1) was then co-infused with either lactated Ringer’s (control) or each site’s respective treatment for 6-min. Following MCh infusion, 20mM N(⍵)-nitro-L-arginine methyl ester (L-NAME) was administered for 60-min to inhibit NOS activity. During, co-infusions either lactated Ringer’s (control) or each site’s respective treatment were continued. After 60-min, MCh (MCh2) co-infusion was administered as before. While at 33°C, 28mM sodium nitroprusside (SNP) was infused for 10-min to determine endothelium-independent vasodilatory responsiveness. Local temperature was then raised to 43°C while SNP infusion continued for 25-min to determine maximal dilatory capacity. CVC was calculated as RBF/mean arterial pressure and normalized to maximal conductance (%CVCmax). MCh responses are reported as the increase from baseline and L-NAME for MCh1 and MCh2, respectively. Nitric oxide contribution was calculated as the difference between MCh1 and MCh2. RESULTS: No difference was observed during MCh1 at the apocynin, allopurinol, or BH4 sites (P \u3e 0.05). Further, no differences were observed between sites for the NO-contribution to dilation (P \u3e 0.05) or maximal dilatory response (P \u3e 0.05). CONCLUSION: These data suggest that attenuated MRMD in BL men in not related to elevated oxidative stress. However, further research is warranted as high- and low-responders to MCh were observed, each group producing seemingly divergent responses to the treatment drugs