Comparing Assessments of Vascular Function via Flow-Mediated Dilation and Rhythmic Handgrip Exercise

Young, otherwise healthy Non-Hispanic Black individuals have been shown to exhibit blunted vascular responsiveness compared to their Non-Hispanic White counterparts, which may be a potential mechanism leading to higher cardiovascular disease risk in this group. Racial differences in vascular function have largely been assessed using flow-mediated dilation (FMD). However, more recent studies have proposed the use of rhythmic handgrip (HG) as an alternative measure of vascular function. PURPOSE: To compare whether rhythmic HG exercise could be an alternative technique to FMD in assessing differences in vascular function between black and white individuals. METHODS: Brachial artery vasodilation was assessed in young healthy black (N = 7; 21 ± 2 years; BMI: 25.5 ± 1.4 kg/m2; mean ± SEM) and white (N = 7; 23 ± 2 years; BMI: 24.0 ± 0.5 kg/m2) men via a standard FMD protocol and rhythmic HG exercise. FMD was assessed by inflating a forearm cuff suprasystolic for 5 min. Rhythmic HG consisted of 3 min HG exercise at 30% of their maximal voluntary contraction (MVC) with a duty cycle of 1-sec contraction/2-sec relaxation. Heart rate (ECG), mean arterial blood pressure (MAP; finger photoplethysmography and automated sphygmomanometer), brachial artery diameter and blood velocity (duplex Doppler ultrasound) were continuously measured during FMD and HG exercise. Brachial artery vasodilation for FMD and rhythmic HG exercise were calculated as a % increase from baseline diameter to peak diameter. RESULTS: Both groups had similar MVCs (black men: 53 ± 1 vs. white men: 54 ± 3 kg; P = 0.80) and resting MAP (black men: 83 ± 2 vs. white men: 85 ± 2 mmHg; P = 0.43). Rhythmic HG dilation (P = 0.72) and FMD (P = 0.43) were not different between groups. Interestingly, white men had greater vasodilation with FMD compared to HG (FMD: 5.76 ± 0.58 vs. HG: 4.13 ± 0.52%; P \u3c 0.01). In contrast, black men had similar vasodilation between FMD and HG (FMD: 4.51 ± 1.01 vs. HG: 4.46 ± 0.89%; P = 0.97). CONCLUSION: These preliminary data suggest that rhythmic HG exercise and FMD provide similar information in the assessment of vascular function between racial groups

Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans

As a primary component of homeostasis, the sympathetic nervous system enables rapid adjustments to stress through its ability to communicate messages among organs and cause targeted and graded end organ responses. Key in this communication model is the pattern of neural signals emanating from the central to peripheral components of the sympathetic nervous system. But what is the communication strategy employed in peripheral sympathetic nerve activity (SNA)? Can we develop and interpret the system of coding in SNA that improves our understanding of the neural control of the circulation? In 1968, Hagbarth and Vallbo (Hagbarth KE, Vallbo AB. Acta Physiol Scand 74: 96–108, 1968) reported the first use of microneurographic methods to record sympathetic discharges in peripheral nerves of conscious humans, allowing quantification of SNA at rest and sympathetic responsiveness to physiological stressors in health and disease. This technique also has enabled a growing investigation into the coding patterns within, and cardiovascular outcomes associated with, postganglionic SNA. This review outlines how results obtained by microneurographic means have improved our understanding of SNA outflow patterns at the action potential level, focusing on SNA directed toward skeletal muscle in conscious humans

Blunted Spontaneous Sympathetic Baroreflex Sensitivity in Young Healthy Black Men

The prevalence and severity of hypertension in black individuals are greater than in any other racial/ethnic group in the United States. The arterial baroreflex dynamically regulates blood pressure (BP) on a beat-to-beat basis via alterations in cardiac output and peripheral vascular resistance, and impairments in arterial baroreflex function are well-documented in patients with hypertension. Previous reports suggest that black individuals have a reduced cardiac baroreflex sensitivity compared to their white counterparts. However, the peripheral sympathetic component of the arterial baroreflex has never been examined in young healthy black individuals. PURPOSE: We sought to compare spontaneous sympathetic baroreflex sensitivity between young healthy black and white men. METHODS: Seven healthy black (age: 20 ± 1 years, BMI: 24.3 ± 1.3 kg/m2) and seven healthy white (age: 22 ± 1 years, BMI: 27.0 ± 1.2 kg/m2) men participated in the study. Heart rate (ECG), beat-to-beat BP (finger photoplethysmography) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were continuously measured during a 20-minute resting period. MSNA was quantified as burst incidence (bursts/100 heartbeats) and averaged over 3-mmHg diastolic BP bins for each individual. The linear relationship between the spontaneous changes in MSNA and diastolic BP was assessed using a weighted linear regression analysis. Sympathetic baroreflex sensitivity was quantified as the slope of MSNA burst incidence to diastolic BP. RESULTS: Heart rate, systolic BP, diastolic BP and mean arterial pressure was not different between the 2 groups (p \u3e 0.05 for all). MSNA burst incidence was also similar between the two groups (black men, 16 ± 2.2 burst/100 heartbeats vs. white men, 21.4 ± 2.0 bursts/100 heartbeats, p = 0.10). The slope of MSNA burst incidence to diastolic BP was significantly lower in black compared to white men (black men, -2.20 ± 0.4 bursts/100 heartbeats/mmHg vs. white men, -3.36 ± 0.3 bursts/100 heartbeats/mmHg, p = 0.03). CONCLUSION: These preliminary data suggest that young healthy black men have a blunted sympathetic baroreflex sensitivity compared to white men

Sex Differences in the Relationship Between Baroreflex Effectiveness Index and Spontaneous Cardiac Baroreflex Sensitivity

Baroreflex effectiveness index (BEI) is a relatively new measure used to assess cardiac baroreflex function. It is unclear whether BEI provides independent or complementary information compared to traditional spontaneous cardiac baroreflex sensitivity (BRS) measures. PURPOSE: The purpose of this project was to begin to explore the relationship between BEI and BRS in young adults and to investigate the impact of sex on these potential relationships. We hypothesized that there would be a positive correlation between BEI and BRS in both males and females. METHODS: We studied 45 young healthy adults, 17 males (24 ± 4 years) and 28 females (23 ± 4 years). Heart rate (ECG) and beat-to-beat arterial blood pressure (finger photoplethysmography) were continuously recorded during a five-minute resting baseline. Spontaneous cardiac BRS was measured using the Sequence Method, by identifying the gain of the relationship between systolic blood pressure and RRI from sequence(s) of three or more consecutive heartbeats in which systolic blood pressure and RRI change in the same direction. BEI was quantified as the ratio of the number of baroreflex-driven ramps relative to all systolic blood pressure ramps. RESULTS: BEI (Male: 0.65 ± 0.14, Female: 0.61 ± 0.13; mean ± SD, p=0.27) and BRS (Male: 21.3 ± 8.4, Female: 27.27 ± 12.6, p=0.09) between groups was not different. There was no significant relationship between BEI and BRS among all participants (r= 0.13, p= 0.36). However, sex-specific analysis data revealed a positive correlation in our male group (r= 0.57, p=0.01), and no relationship in our female group (r= 0.03, p=0.84). CONCLUSION: These preliminary data suggest that the relationship between BEI and BRS may be sex-dependent

Exploring the Potential Role of Family History of Hypertension on Racial Differences in Sympathetic Vascular Transduction

The prevalence of hypertension in Non-Hispanic Black (BL) men surpasses all other racial groups. Our laboratory has previously demonstrated exaggerated vasoconstrictor and blood pressure (BP) responses to spontaneous bursts of muscle sympathetic nerve activity (MSNA; sympathetic vascular transduction) in young, healthy BL men compared to their Non-Hispanic White (WH) counterparts. Because a family history of hypertension (FHH) further compounds cardiovascular risk, we wanted to begin to explore the potential impact of a positive (+) FHH on sympathetic vascular transduction. Whether a +FHH influences sympathetic vascular transduction in WH and/or BL men remains unknown. PURPOSE: To begin to explore if +FHH influences sympathetic vascular transduction within and between racial groups. METHODS: 22 men, nine with a +FHH (4 BL men) and 13 without a FHH (-FHH; 6 BL men) were recruited. Beat-to-beat BP (Finometer), femoral artery blood flow (Doppler ultrasound), and MSNA were measured during a 20-minute quiet rest. The mean BP and leg vascular conductance (LVC; blood flow/mean BP) responses to spontaneous bursts of MSNA were quantified via a signal averaging technique. RESULTS: Resting heart rate, BP, and MSNA were not significantly different between groups (all p\u3e0.05). As previously demonstrated by our laboratory, the BL men exhibited an augmented sympathetic vascular transduction compared to the WH men (e.g., peak BP response, WH men: Δ4.1±0.3, BL men: Δ5.6±0.7 mmHg, p=0.04). When accounting for FHH within the groups, the peak BP (WH +FHH: Δ4.4±0.6 vs. WH -FHH: Δ3.8±0.4 mmHg, p=0.4) and nadir LVC responses (WH +FHH: Δ-0.5±0.07 vs. WH -FHH: Δ-0.5±0.09 ml·min-¹·mmHg-¹, p=0.7) were not significantly different between WH men +FHH and WH men –FHH. Likewise, the BL men +FHH exhibited similar peak BP (BL +FHH: Δ6.2±0.7 vs. BL -FHH: Δ5.3±1.1 mmHg, p=0.5) and nadir LVC (BL +FHH: Δ-1.1±0.44 vs. BL -FHH: Δ-0.6±0.10 ml·min-¹·mmHg-¹, p=0.2) responses to bursts of MSNA compared to the BL men –FHH. CONCLUSION: These preliminary findings do not support a role for +FHH in augmented sympathetic vascular transduction, therefore suggesting that racial differences in sympathetic vascular transduction are independent of FHH

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

Quantification of Sympathetic Transduction in Type 2 Diabetes Patients

Type 2 Diabetes patients (T2D) have been shown to have greater alpha­-adrenergic sensitivity. How this impacts the transduction of muscle sympathetic nerve activity (MSNA) to arterial blood pressure under resting conditions using spontaneous fluctuations in MSNA, as well as during stressors known to elicit sympatho­-excitation (e.g., cold pressor test (CPT)) is unclear. PURPOSE: We tested the hypothesis that T2D patients would exhibit greater sympathetic transduction compared to age­ and BMI­-matched, healthy controls. METHODS: MSNA (microneurography), heart rate (ECG), and beat­-to­-beat arterial blood pressure (finger photoplethysmography) were continuously recorded during a 10 minute baseline period, and in response to a 2­minute CPT in six T2D patients and six age­ and BMI­-matched, healthy controls (CON).To quantify sympathetic transduction at rest, normalized burst heights were divided into four quartiles (smallest to largest), related to the corresponding peak change in mean arterial pressure (MAP) within those quartiles and a slope was determined. To quantify sympathetic transduction in response to a stressor, the change in MAP was related to the change in MSNA from rest to the last minute of CPT. RESULTS: There were no differences in resting sympathetic transduction between groups (CON slope: 0.0103±0.0023 mmHg/AU, T2D slope: 0.0095±0.0016 mmHg/AU; p=0.78). Indeed, signal averaging of MSNA bursts indicated a similar peak increase in blood pressure in CON (+4.2±0.6 mmHg) and T2D (+4.0±0.9 mmHg) (p=0.66). Although the peak increase in blood pressure to CPT tended to be higher in T2D (T2D: +31.6±3.4 mmHg, CON: +21.4±3.7 mmHg; p=0.096), the Δ MAP/ Δ MSNA relationship during CPT was not different between groups (CON: 0.4158±0.21, T2D: 0.1862±0.05; p=0.36). CONCLUSIONS: Despite clear sympathetically-­mediated increases in blood pressure in T2D patients and healthy CON subjects both at rest and during the CPT, neither of the methodologies used to estimate sympathetic transduction, with respect to changes in arterial blood pressure, detected group differences

Effects of statins on metabolic adaptations to aerobic exercise training : preliminary findings [abstract]

Emerging evidence suggests statins, unlike exercise, may cause deleterious effects on skeletal muscle oxidative capacity and insulin sensitivity. The purpose of this study was to determine if daily statin therapy altered the ability of exercise to lower fasting plasma insulin and glucose and improve cardiorespiratory fitness

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

Pressor and Sympathetic Responses to Graded Skeletal Muscle Metaboreflex Activation in Females with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease characterized by demyelination in the central nervous system which disproportionately impacts females. Previous studies suggest MS-related exercise intolerance may be due to abnormal control of arterial blood pressure (BP) via the skeletal muscle metaboreflex. However, few studies have been performed and equivocal results reported. Discontinuity in prior data may be due to limited perturbation of metaboreflex activation using only low and moderate intensity exercise. PURPOSE: The purpose of this investigation was to test the hypothesis that females with MS have blunted BP and sympathetic responses to graded static handgrip (HG) exercise and isolated metaboreflex activation during postexercise ischemia (PEI) compared to healthy controls. METHODS: In 7 females with relapsing-remitting MS and 9 healthy female controls beat-to-beat BP (finometer) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were recorded at rest and during two minutes of handgrip performed at 30% and 40% maximum voluntary contraction followed by two minutes of PEI to isolate the muscle metaboreflex. RESULTS: There were no differences in resting mean arterial pressure (MAP; P= 0.16) or MSNA burst frequency (P= 0.15) between MS and controls. MAP and MSNA increased during 30% HG (MS: Δ19.8 ± 9.1 mmHg vs. Con: Δ17.8 ± 5.4 mmHg; P= 0.30 and MS: Δ17 ± 12 bursts/min vs. Con: Δ18 ± 17 bursts/min; P= 0.46) and 40% HG (MS: Δ29.3 ± 8.0 mmHg vs. Con: Δ30.0 ± 6.9 mmHg; P= 0.43 and MS: Δ36 ± 16 bursts/min vs. Con: Δ40 ± 9 bursts/min; P= 0.30) with no differences between groups. Likewise, MAP and MSNA responses were also not different during PEI post 30% HG (MS: Δ15.8 ± 7.6 mmHg vs. Con: Δ15.8 ± 6.4 mmHg; P= 0.50 and MS: Δ15 ± 9 bursts/min vs. Con: Δ11 ± 7 bursts/min; P= 0.19) or PEI post 40% HG (MS: Δ25.8 ± 6.3 mmHg vs. Con: Δ22.6 ± 8.2 mmHg; P= 0.43 and MS: Δ23 ± 13 bursts/min vs. Con: Δ24 ± 7 bursts/min; P= 0.46) between MS and controls. CONCLUSION: These preliminary data suggest intact skeletal muscle metaboreflex control of arterial BP in females with MS