Relationship Between Arterial Stiffness and Cerebral Vascular Reactivity in College-aged African Americans

African Americans (AA) have increased risk for cardio and cerebral vascular disease relative to Caucasians (CA). While is it generally accepted that arteries become stiffer at a younger age in AA; less is known regarding cerebral vascular function / reactivity (CVMR) to hypercapnia in AAs. Furthermore, to our knowledge, little is known regarding the relationship between arterial stiffness and CVMR, particularly in young healthy adults. We tested the hypothesis that AAs have elevated arterial stiffness and reduced CVMR during hypercapnia relative to CAs. Furthermore, we hypothesized that there would be a negative relationship between arterial stiffness and CVMR. In 7 AA and 13 CA subjects central arterial stiffness was indexed from carotid-femoral pulse wave velocity (PWV). CVMR was assessed by the cerebral vascular conductance (CVC) response to rebreathing induced hypercapnia. PWV was elevated in the AAs (AA: 564±54 cm/ms vs. CA: 482±73 cm/ms; P=0.02). CVMR was also significantly reduced during hypercapnic rebreathing in the AAs (AA: 2.7±0.7 % / Torr vs. CA: 4.0±1.1 % / Torr; P=0.01). When data from all subjects was included there was a negative relationship between PWV and CVMR such those with elevated stiffness had an attenuated increase in CVC during hypercapnia (P=0.02). These data indicate that AAs have impaired cerebral vascular responses to hypercapnia and that this might be related to stiffer arteries

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 Natural Cocoa Consumption Improves Cerebral Vasodilatory Capacity in Obese Individuals

Obesity increases the risk for cardio and cerebral vascular diseases including hypertension, coronary artery disease, and stroke. Our preliminary data indicate that obese individuals (Obese) have attenuated cerebral vasodilatory capacity compared to age / sex matched lean individuals (Lean). This study tested the hypothesis that natural cocoa (NC) consumption (13g NC, The Hershey Company) would restore cerebral vasodilatory capacity in Obese. 15 lean (BMI \u3c 25) and 15 obese (BMI \u3e 30) subjects underwent a rebreathing protocol while cerebral blood velocity (CBFV) was measured before and 2 hr post consumption of a NC-containing drink or a NC-free placebo (randomized order, single-blinded). Cerebral vascular conductance (CVCI) was calculated as CBFV / MAP. The response to rebreathing was expressed as % of baseline CVCI (% CVCI). Prior to beverage consumption, the range of % CVCI and the maximal increase in CVCI in response to rebreathing-induced hypercapnia was attenuated in Obese (P0.05 pre vs. post), such that the baseline differences between groups were eliminated (P\u3e0.05). The placebo beverage had no effect on any indices of cerebral vascular function in either cohort (P\u3e0.05 for all variables). These data support the hypothesis that NC consumption can acutely augment cerebral vasodilatory capacity in Obese

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

Inter-individual Differences in Tolerance to a Simulated Hemorrhage Challenge During Heat Stress: Cerebrovascular Control

A high degree of inter-individual variability exists in heat stress (HS) -induced reductions in orthostatic tolerance relative to normothermia (NT), which may be associated with HS-mediated reductions in cerebral perfusion, and thus mechanisms of cerebrovascular control during hypotensive challenges. This study tested two hypotheses; 1) the magnitude of increase in cerebral autoregulation (CA) would be negatively correlated with the difference in tolerance to graded lower body negative pressure (LBNP) 30 [assessed with a cumulative stress index (CSI)] during HS relative to NT (CSIdiff), and 2) cerebrovascular sensitivity to HS-induced hypocapnia would be positively correlated with CSIdiff. Subjects (N=13) were exposed to LBNP on two occasions (NT and HS) separated by \u3e72h to assess CSI. On a third day, indices of CA were assessed during NT and HS by spectral and transfer function analyses, and cerebrovascular sensitivity to changes in PaCO2 was determined during NT, HS, and HS+LBNP (-20 mm Hg; HSLBNP). Estimates of CA were improved during HS compared to NT (P0.05). Hyperventilation-induced hypocapnia reduced cerebral vascular conductance (CVCi) during HS and HSLBNP relative to NT (P0.05 for all). In summary, HS augments mechanisms of cerebrovascular control to protect against orthostatic challenges; however, individual differences in these responses do not predict tolerance to a simulated hemorrhage when internal temperature is elevated

Cerebral and peripheral microvascular function in individuals with elevated cardiovascular disease risk

textThe series of studies in this dissertation determined: 1) the effectiveness of a clinically applicable dietary supplement on cerebral vascular function in African Americans (AA), 2) cerebral vascular function in obese individuals, and 3) the underlying mechanism of cutaneous microvascular dysfunction in AA. Study #1 identified that acute flavanol consumption improves cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia in AA. Our laboratory previously found that hypercapnia-induced cerebral vasodilation is reduced in AA when compared with Caucasian Americans (CA). Findings in study #1 may provide an effective interventional strategy to mitigate the high incidence of cerebral vascular diseases, which is commonly found in AA. Study #2 assessed the cerebral vasodilatory capacity in obese individuals. Cerebral vasodilation during hypercapnia, as indexed by the total range of change and the maximal increase in cerebral vascular conductance, was decreased in obese individuals relative to lean counterparts. This attenuated response in obese individuals may explain why they are at higher risk for cerebral vascular diseases including Alzheimer’s disease and stroke. In study #3, mechanisms underlying impaired cutaneous microvascular thermal reactivity in AA were explored using an intradermal microdialysis technique. Our preliminary data previously found that cutaneous vasodilation in response to local heating is decreased in AA. As a follow-up study, we assessed cutaneous vasodilation using pharmacological agents ascorbic acid and tempol, a global antioxidant and superoxide-specific scavenger, respectively. Study #3 determined that reduced cutaneous microvascular thermal reactivity in AA is mainly due to elevated concentration/activity of superoxide. Collectively, the series of studies in the current dissertation provide a potential therapeutic strategy to ameliorate the vascular impairment as well as potential mechanisms for elevated cerebral and peripheral vascular dysfunction in individuals with elevated risk of cardiovascular diseases for future clinical/mechanistic investigations.Kinesiology and Health Educatio

Impaired cerebral vascular function in college-aged African Americans and Caucasian Americans : potential role of Vitamin D and arterial stiffness

textAfrican Americans have increased risk for cardiovascular and cerebral vascular disease relative to Caucasian Americans. While it is generally accepted that arteries become stiffer at a younger age in African Americans; less is known regarding cerebral vascular function / reactivity (CVMR) to hypercapnia in African Americans. Furthermore, little is known regarding the relationship between arterial stiffness and CVMR, particularly in young healthy adults. We hypothesized that African Americans have stiffer arteries (i.e. arterial stiffness) and reduced CVMR during hypercapnia relative to Caucasian Americans. We also hypothesized that there would be a negative relationship between arterial stiffness and CVMR. Lastly, we hypothesized that these responses would be related to a decrease in Vitamin D status in this population and there would be correlation between Vitamin D status and CVMR. In 11 African American and 19 Caucasian American subjects central arterial stiffness was indexed from carotid-femoral pulse wave velocity (PWV). CVMR was assessed by the cerebral vascular conductance (CVC) response to rebreathing-induced hypercapnia. Vitamin D status was assessed from plasma 25(OH) Vitamin D. PWV was elevated in the African Americans (African American: 581.16 ± 27.7 cm/sec vs. Caucasian American: 502.98 ± 17.6 cm/sec; P < 0.01). CVMR was significantly reduced during hypercapnic rebreathing in the African Americans (African American: 3.05 ± 0.38% of baseline/mmHg vs. Caucasian American: 5.09 ± 0.29% of baseline/mmHg; P < 0.001). When data from all subjects was included there was a trend towards a negative relationship (R = 0.32, P = 0.10) between PWV and CVMR. Vitamin D status was significantly lower in African Americans (African American: 14.96 ± 0.97 ng/ml vs. Caucasian American: 32.73 ± 0.99 ng/ml; P < 0.001); however, there was no significant relationship between Vitamin D status and CVMR (R = 0.23 P = 0.23). In conclusion, these data indicate that African Americans have impaired cerebral vascular responses to hypercapnia, stiffer arteries, and lower Vitamin D status when compared with Caucasian Americans. In addition, there may be a negative relationship between CVMR and PWV; however, no significant correlation between Vitamin D status and vascular function including PWV or CVMR was observed in this study.Kinesiology and Health Educatio

Sympathetic Overactivity Contributes to the Pathogenesis of Non-alcoholic Fatty Liver Disease During Diet-induced Obesity

Non-alcoholic fatty liver disease (NAFLD) is associated with the development of obesity and is a significant contributor to chronic liver, metabolic, and cardiovascular diseases. We have recently shown that hepatic sympathetic nerve activity is significantly elevated in mice fed a high fat diet (HFD; 33±2 vs. 63±5 spikes/s, normal chow vs. HFD; p\u3c0.05), although the contribution of the sympathetic nervous system to NAFLD pathology remains unclear. Therefore, we tested the hypothesis that sympathetic overactivity contributes to NAFLD during diet-induced obesity. Male C57B1/6 mice were fed a HFD (60% fat) or normal chow (5% fat) for 15 weeks. 6-hydroxydopamine (6-OHDA, 150 mg/kg i.p.) was then administered to selectively destroy sympathetic nerves, or vehicle control (n=4/group), and mice were sacrificed 3 days later. 6-OHDA treatment did not influence body weight (e.g. 41±3 vs. 40±2 g; HFD-vehicle vs. HFD-OHDA; p\u3e0.05) or visceral adipose tissue mass in normal chow or HFD fed animals. However, HFD resulted in significant increases in liver weight (1.0±0.1 vs. 1.8±0.1 g normal chow-vehicle vs. HFD-OHDA; p\u3c0.05) and selective ablation of sympathetic nerves rescued HFD-induced hepatomegaly (1.3±0.2 g; p\u3e0.05 vs. normal chow). In line with this, histological examination (H&E staining) revealed widespread hepatic lipid accumulation in HFD fed mice, which was reduced to normal levels following 6-OHDA administration (figure). Diet-induced obesity also resulted in elevations in plasma glucose (172±13 vs. 249±20 mg/dl; normal chow-vehicle vs. HFD-vehicle; p\u3c0.05), and ablation of sympathetic nerves restored HFD-mediated hyperglycemia (160±7 mg/dl; HFD-OHDA; p\u3e0.05 vs. normal chow). Concomitant with this, 6-OHDA administration in HFD fed animals was associated with a reduction in hepatic mRNA markers of gluconeogenesis (e.g. G6PC 6.6±1.0 vs. 3.2±0.7 fold normal chow-vehicle; HFD-vehicle vs. HFD-OHDA; p\u3c0.05) and lipogenesis (e.g. Srebp-1c 2.0±0.3 vs. 0.8±0.3 fold normal chow-vehicle; HFD-vehicle vs. HFD-OHDA; p\u3c0.05). Collectively, these findings demonstrate that removal of sympathetic nerve activity rescues obesity-induced hepatomegaly, hepatic steatosis and hyperglycemia, independent of an effect on body weight and adiposity. Moreover, this data reveals a novel role for the sympathetic nervous system in HFD-mediated NAFLD and suggest that targeting hepatic sympathetic overactivity may represent a novel therapeutic approach to treat NAFLD