Relationship Between 25(OH) Vitamin D3 and Cerebral Vascular Reactivity in College-aged African and Caucasian Americans

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Attenuated Cerebral Vasodilatory Capacity in Response to Hypercapnia in Young Obese Individuals

Obese individuals are at a greater risk for the development of a variety of cardio and cerebral vascular diseases including hypertension, atherosclerosis, coronary artery disease and stroke. Furthermore, obesity is associated with cognitive impairment and is a risk factor for dementia and Alzheimer’s disease. The exact mechanisms of this elevated risk are not fully characterized; however, impaired microvascular function is believed to be a contributor. This study tested the hypothesis that the cerebral vasodilatory capacity in response to hypercapnia is reduced in obese individuals relative to age and sex matched lean counterparts. Cerebral blood velocity (CBFV) was measured using transcranial Doppler before and during rebreathing-induced hypercapnia in obese (Obese, n=14) and lean (Lean, n=14) subjects. Cerebral vascular conductance (CVCI) was calculated as CBFV / mean arterial pressure (MAP), and a four parameter logistic regression was applied for sigmoidal curve fitting of the relationship between % change in CVCI and end-tidal CO2 tension (PETCO2). The magnitude of hypercapnia (Δ PETCO2) during rebreathing was similar between groups (Obese 14 ± 3 mmHg vs. Lean: 15 ± 2 mmHg; P = 0.13). The maximum increase in CVCI (Obese: 155 ± 17% vs. Lean: 176 ± 23%; P \u3c 0.05) and the total range of change in CVCI (Obese: 50 ± 15% vs. Lean: 75 ± 22%; P \u3c 0.01) during rebreathing were reduced in the obese relative to the lean individuals. These data indicate that cerebral vasodilatory capacity in response to changes in PETCO2 during hypercapnia is attenuated in obese individuals compared with lean individuals

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

Examining the Effect of Exogenous Ketone Supplement on Indices of Peripheral Vascular Health/Function

Cardiovascular disease (CVD) remains the leading cause of death in the US and worldwide. The risk for and prevalence of CVD are elevated by various factors including impaired micro- and macrovascular function. Associated mechanisms are multifactorial but are related to elevated oxidative stress and/or inflammation which contribute to reduced nitric oxide bioavailability and ultimately vasodilatory reactivity. Ketogenic diets, commonly used as a strategy to lose weight and improve health, have been reported to improve mitochondria function, as well as antioxidant and inflammatory status. To the best of our knowledge, the effects on vascular function are less understood. PURPOSE: This study tested the hypothesis that 14-days of increased daily Ketone supplementation would improve well-validated indices of peripheral micro and macrovascular function in otherwise young healthy adults. METHODS: Six young healthy adults (4 males; age: 22±4 yr.; BMI 24±3 kg/m2) have participated thus far. All measures were assessed at baseline and after 14-days of increased Ketone supplementation which was accomplished by adding ~13.7 g of Keto5 XOGenius powder to 16oz of water twice daily. Keto5 XOGenius contains increased levels of ketone body, e.g., β-hyroxybutyrate which have antioxidant and anti-inflammatory properties as well as neuroprotective effects. Peripheral macro and microvascular function/health were assessed before (baseline) and after Keto5 XOGenius supplementation as vasodilation in the brachial artery (flow mediated vasodilation; %FMD) and reactive hyperemia (peak mean forearm blood velocity (FBVmean)) in the forearm vasculature respectively following 5-min of forearm ischemia induced by suprasystolic cuff occlusion. RESULTS: Peripheral macrovascular function assessed as %FMD tended to be augmented following Keto5 XOGenius supplementation (Pre: 2.3±1.6% vs. Post: 3.8±1.8%, P=0.05). Whereas peripheral microvascular function assessed as peak FBVmean was NOT different following the intervention (Pre: 67±12 cm·s-1 vs. Post: 66±20 cm·s-1, P=0.88). Conclusion: These preliminary data indicate a positive effect of Keto5 XOGenius supplementation on peripheral macrovascular function/health. Future studies will continue to expand upon these findings in a larger cohort of individuals

Within-Day Repeatability of Cerebral Vasomotor Reactivity to Rebreathing-Induced Hypercapnia: Impact of a 15 Minute Recovery

Cerebral vasodilatory responsiveness to elevations in arterial carbon dioxide concentration, termed cerebral vasomotor reactivity (CVMR), is utilized to assess cerebral vascular function and health. An impairment in this response is associated with risk for various cerebral vascular diseases and neurocognitive conditions including stroke, cognitive dysfunction, dementia, and Alzheimer’s disease. One commonly utilized methodological approach to assess CVMR is to induce transient hypercapnia by having the participant rebreathe their own expired air. We recently reported very good within-day repeatability when two trials were separated by 2 hr. However, in research protocols, repeat assessments are commonly separated by a shorter duration (i.e., 15 min) that is typically tied to the return of hemodynamic variables (heart rate, arterial blood pressure, etc.) to baseline values. PURPOSE: To determine the within-day repeatability of CVMR responses to rebreathing-induced hypercapnia when trials are separated by 15 min.METHODS: Eight young healthy males (age: 23 ± 3 years, BMI: 24.4 ± 2.3 kgm-2) were studied following a minimum 4 hour fast. All participants underwent two trials of rebreathing-induced hypercapnia separated by 15 min. Heart rate (ECG), respiration (Pneumotrace), beat-to-beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv; transcranial Doppler) and breath-by-breath end-tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv divided by mean arterial blood pressure. CVMR was assessed as the slope of the linear regression between the increase in %MCAv and %CVCi during hypercapnia. The increase in %MCAv and %CVCi was also assessed at a ΔPETCO2 of 15 mmHg. RESULTS: The slope of %MCAv vs ΔPETCO2 demonstrated poor to excellent repeatability between the 2 rebreathing-induced hypercapnia trials (Trial 1: 3.3 ± 1.1 %mmHg−1; Trial 2: 2.7 ± 1.5 %mmHg−1; ICC = 0.84 [0.26–0.97, p = 0.008). The slope of %CVCi vs. ΔPETCO2 showed good to excellent repeatability (Trial 1: 2.2 ± 1.0 %mmHg−1; Trial 2: 2.1 ± 1.1 %mmHg−1; ICC = 0.92 [0.65–0.99], p = 0.002). At a ΔPETCO2 of 15 mmHg from baseline, the % increase in MCAv exhibited poor to excellent repeatability (Trial 1: 45 ± 17%; Trial 2: 37 ± 18%; ICC: 0.87 [0.26–0.97], p = 0.003), while the % increase in CVCi also demonstrated poor to excellent repeatability (Trial 1: 33 ± 15%; Trial 2: 28 ± 12%; ICC: 0.70 [-0.38–0.94], p = 0.069). CONCLUSION: These preliminary results suggest that a 15 min recovery between hypercapnia perturbations may not be sufficient in all subjects. While we found good within day repeatability in 4 out of 8 subjects, highly variable responses were found among other individuals. These data are important when considering protocol designs for examining cerebral vasomotor reactivity

Relationships Between Indices of Macrovascular and Microvascular Function in Young, Black Women

Blacks (BL) exhibit an exaggerated prevalence of and mortality from cardiovascular disease (CVD) relative to other populations. Macro- and microvascular dysfunction is often a hallmark of heightened CVD risk, with both demonstrated in BL. However, data regarding this dysfunction remains sparse, particularly in BL women. Common indices of vascular function include flow-mediated dilation (FMD) and reactive hyperemia (RH) following a brief period of suprasystolic cuff occlusion and cutaneous thermal reactivity to local heating (LH). However, the relationship between these indices has not been established in BL women. PURPOSE: The present study aimed to test the relationship between indices of vascular function in BL women as assessed by FMD, RH, and LH. METHODS: To test this hypothesis, 6 white women (WW) and 6 BW (age: 22±2 vs. 21±3, respectively) were studied. FMD and RH were assessed following a period of suprasystolic cuff occlusion. Briefly, a rapid inflation cuff was secured just distal to the antecubital fossa for arterial occlusion. Blood velocity (Vmean; cm ∙ s-1) and vessel diameter (d; mm) were measured continuously via high-resolution, duplex Doppler ultrasound during a 2-min baseline, 5-min of cuff occlusion, and 3-min of recovery. FMD was determined as the percent dilation from baseline (%FMD) while RH was determined as the peak and area under the curve (AUC) responses for shear rate (8 ∙ Vmean ∙ d-1) and blood flow (Vmean ∙ π ∙ (d ∙ 20-1)2 ∙ 60). Cutaneous thermal reactivity was assessed using laser-Doppler flowmetry during a standard LH protocol and reported as cutaneous vascular conductance (CVC; red blood cell flux/mean arterial pressure). Following a baseline with local skin temperature clamped at 33°C, a 39°C heat stimulus was applied to induce cutaneous vasodilation for ~30-min. The sustained vasodilation at the end of heating is predominantly nitric oxide mediated and provides an index of microvascular function. As the LH component served as part of a larger intradermal microdialysis protocol, maximal blood flow responses were elicited via combined intradermal sodium nitroprusside (28mM) infusion and 43°C heating. CVC during the 39°C plateau was normalized to maximal CVC (%CVCmax) to account for intersite variability. Pearson correlations were then performed between the FMD, RH, and LH responses. RESULTS: Significant relationships were observed between %FMD and shear AUC (r = 0.89; P = 0.02), and blood flow AUC (r = 0.92; P = 0.01) in WW, but not in BW (r = 0.63; P = 0.18 and r = -0.24; P = 0.65, respectively). However, neither FMD nor RH correlated with the cutaneous blood flow responses to LH (P \u3e 0.05) in either WW or BW. CONCLUSION: These preliminary data suggest that FMD is highly correlated to some indices of RH in WW, but that this relationship does not hold in BW. Further, there appears to be no relationship between microvascular function as assessed by RH and LH in either population

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

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

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