HDL-C and apolipoprotein A-I are independently associated with skeletal muscle mitochondrial function in healthy humans.

Prior animal and cell studies have demonstrated a direct role of high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-I) in enhancing skeletal muscle mitochondrial function and exercise capacity. However, the relevance of these animal and cell investigations in humans remains unknown. Therefore, a cross-sectional study was conducted in 48 adults (67% female, 8% Black participants, age 39 ± 15.4 yr old) to characterize the associations between HDL measures, ApoA-I, and muscle mitochondrial function. Forearm muscle oxygen recovery time (tau) from postexercise recovery kinetics was used to assess skeletal muscle mitochondrial function. Lipoprotein measures were assessed by nuclear magnetic resonance. HDL efflux capacity was assessed using J774 macrophages, radiolabeled cholesterol, and apolipoprotein B-depleted plasma both with and without added cyclic adenosine monophosphate. In univariate analyses, faster skeletal muscle oxygen recovery time (lower tau) was significantly associated with higher levels of HDL cholesterol (HDL-C), ApoA-I, and larger mean HDL size, but not HDL cholesterol efflux capacity. Slower recovery time (higher tau) was positively associated with body mass index (BMI) and fasting plasma glucose (FPG). In multivariable linear regression analyses, higher levels of HDL-C and ApoA-I, as well as larger HDL size, were independently associated with faster skeletal muscle oxygen recovery times that persisted after adjusting for BMI and FPG (all P < 0.05). In conclusion, higher levels of HDL-C, ApoA-I, and larger mean HDL size were independently associated with enhanced skeletal muscle mitochondrial function in healthy humans.NEW & NOTEWORTHY Our study provides the first direct evidence supporting the beneficial role of HDL-C and ApoA-I on enhanced skeletal muscle mitochondrial function in healthy young to middle-aged humans without cardiometabolic disease.

Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. METHODS: Electrocardiogram and beat-to-beat blood pressure were continuously recorded during 8-10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. RESULTS: Groups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). CONCLUSION: These data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

Aging and sympathetic transduction to blood pressure in humans: methodological and physiological considerations.

Recent reports suggest that quantification of signal-averaged sympathetic transduction is influenced by resting muscle sympathetic nerve activity (MSNA) and burst occurrence relative to the average mean arterial pressure (MAP). Herein, we asked how these findings may influence age-related reductions in sympathetic transduction. Beat-to-beat blood pressure and MSNA were recorded during 5 min of rest in 27 younger (13 females: age, 25 ± 5 yr; BMI, 25 ± 4 kg/m2) and 26 older (15 females: age, 59 ± 5 yr; BMI, 26 ± 4 kg/m2) healthy adults. All MSNA bursts were signal averaged together. Beat-to-beat MAP values were then split into low (T1), middle (T2), and high (T3) tertiles, and signal-averaged transduction was calculated within each tertile. Resting MSNA was higher in older adults and MAP was similar between groups. Older adults exhibited blunted overall MAP transduction (younger, Δ1.5 ± 0.6 vs. older, Δ0.9 ± 0.7 mmHg; P = 0.005), which was irrespective of relation to prevailing MAP. A greater proportion of bursts occurred above the average MAP in older adults (P < 0.001), and a larger proportion of these bursts were associated with depressor responses (P = 0.005). Nonetheless, assessment of bursts above the average MAP associated with pressor responses revealed similar age-associated reductions in transduction (younger, Δ2.6 ± 1.6 vs. older, Δ1.7 ± 0.8 mmHg; P = 0.016). These findings indicate an age-related increase in burst occurrence above the average resting MAP, which alone does not explain blunted transduction, thereby supporting the physiological underpinnings of age-related decrements in sympathetic transduction to blood pressure.NEW & NOTEWORTHY The current study demonstrated that aging is associated with a greater prevalence of sympathetic bursts occurring above the average blood pressure, which offers both methodologically and physiologically relevant information regarding aging and sympathetic control of blood pressure. These data support age-related reductions in sympathetic transduction via a reduced pressor response to sympathetic bursts irrespective of the prevailing absolute blood pressure value, along with increases in sympathetic outflow necessary to maintain blood pressure.

Sympathetic transduction at rest and during cold pressor test in young healthy non-Hispanic Black and White women.

Non-Hispanic Black (BL) individuals have the highest prevalence of hypertension and cardiovascular disease (CVD) compared with all other racial/ethnic groups. Previous work focused on racial disparities in sympathetic control and blood pressure (BP) regulation between young BL and White (WH) adults, have mainly included men. Herein, we hypothesized that BL women would exhibit augmented resting sympathetic vascular transduction and greater sympathetic and BP reactivity to cold pressor test (CPT) compared with WH women. Twenty-eight young healthy women (BL: n = 14, 22 [Formula: see text] 4 yr; WH: n = 14, 22 [Formula: see text] 4 yr) participated. Beat-to-beat BP (Finometer), common femoral artery blood flow (duplex Doppler ultrasound), and muscle sympathetic nerve activity (MSNA; microneurography) were continuously recorded. In a subset (BL n = 10, WH n = 11), MSNA and BP were recorded at rest and during a 2-min CPT. Resting sympathetic vascular transduction was quantified as changes in leg vascular conductance (LVC) and mean arterial pressure (MAP) following spontaneous bursts of MSNA using signal averaging. Sympathetic and BP reactivity were quantified as changes in MSNA and MAP during the last minute of CPT. There were no differences in nadir LVC following resting MSNA bursts between BL (-8.70 ± 3.43%) and WH women (-7.30 ± 3.74%; P = 0.394). Likewise, peak increases in MAP following MSNA bursts were not different between groups (BL: +2.80 ± 1.42 mmHg; vs. WH: +2.99 ± 1.15 mmHg; P = 0.683). During CPT, increases in MSNA and MAP were also not different between BL and WH women, with similar transduction estimates between groups (ΔMAP/ΔMSNA; P = 0.182). These findings indicate that young, healthy BL women do not exhibit exaggerated sympathetic transduction or augmented sympathetic and BP reactivity during CPT.NEW & NOTEWORTHY This study was the first to comprehensively investigate sympathetic vascular transduction and sympathetic and BP reactivity during a cold pressor test in young, healthy BL women. We demonstrated that young BL women do not exhibit exaggerated resting sympathetic vascular transduction and do not have augmented sympathetic or BP reactivity during cold stress compared with their WH counterparts. Collectively, these findings suggest that alterations in sympathetic transduction and reactivity are not apparent in young, healthy BL women.

Acute effects of ß-hydroxybutyrate on left ventricular function in young, healthy adults.

Interest in ketones as a cardiac "super fuel" has grown significantly following reports of a marked increase in cardiac output after exogenous ketone administration in heart failure. However, the extent to which this increase in cardiac output is related to changes in cardiac contractility, and dependent on the presence of heart failure, remains incompletely understood. Therefore, we performed a randomized, double-blind, placebo-controlled study of oral ketone ester in young healthy volunteers. Baseline cardiac magnetic resonance imaging was performed and repeated every 15 min for 60 min after ketone and placebo ingestion to assess changes in left ventricular function. As expected, circulating ß-hydroxybutyrate increased rapidly after ketone ingestion, but did not change with placebo (interaction: P < 0.001). Consistent with prior investigations, ketone ingestion resulted in an average 1 L/min increase in cardiac output after 60 min that did not occur with placebo (interaction: P = 0.026). This increase in cardiac output was primarily driven by an increase in heart rate after ketone ingestion (interaction: P = 0.018), with only a modest increase in stroke volume (interaction: P = 0.037). Changes in left ventricular strain and twist mechanics were limited. Taken together, the increase in cardiac output following an acute elevation in circulating ß-hydroxybutyrate is primarily driven by changes in cardiac chronotropy, with minimal inotropic contribution.NEW & NOTEWORTHY In this randomized, double-blind, placebo-controlled study of oral ketone ester in young healthy volunteers, we show a marked increase in cardiac output (∼1 L/min), driven primarily by changes in chronotropy. The cardiac magnetic resonance imaging data support the limited role for inotropy.

Sympathetic transduction to blood pressure during euglycemic-hyperinsulinemia in young healthy adults: role of burst amplitude.

Insulin acts centrally to stimulate sympathetic vasoconstrictor outflow to skeletal muscle and peripherally to promote vasodilation. Given these divergent actions, the "net effect" of insulin on the transduction of muscle sympathetic nerve activity (MSNA) into vasoconstriction and thus, blood pressure (BP) remains unclear. We hypothesized that sympathetic transduction to BP would be attenuated during hyperinsulinemia compared with baseline. In 22 young healthy adults, MSNA (microneurography), and beat-to-beat BP (Finometer or arterial catheter) were continuously recorded, and signal-averaging was performed to quantify the mean arterial pressure (MAP) and total vascular conductance (TVC; Modelflow) responses following spontaneous bursts of MSNA at baseline and during a euglycemic-hyperinsulinemic clamp. Hyperinsulinemia significantly increased MSNA burst frequency and mean burst amplitude (baseline: 46 ± 6 au; insulin: 65 ± 16 au, P < 0.001) but did not alter MAP. The peak MAP (baseline: 3.2 ± 1.5 mmHg; insulin: 3.0 ± 1.9 mmHg, P = 0.67) and nadir TVC (P = 0.45) responses following all MSNA bursts were not different between conditions indicating preserved sympathetic transduction. However, when MSNA bursts were segregated into quartiles based on their amplitudes at baseline and compared with similar amplitude bursts during hyperinsulinemia, the peak MAP and TVC responses were blunted (e.g., largest burst quartile: MAP, baseline: Δ4.4 ± 1.7 mmHg; hyperinsulinemia: Δ3.0 ± 0.8 mmHg, P = 0.02). Notably, ∼15% of bursts during hyperinsulinemia exceeded the size of any burst at baseline, yet the MAP/TVC responses to these larger bursts (MAP, Δ4.9 ± 1.4 mmHg) did not differ from the largest baseline bursts (P = 0.47). These findings indicate that increases in MSNA burst amplitude contribute to the overall maintenance of sympathetic transduction during hyperinsulinemia.

Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis.

Emerging evidence suggests that COVID-19 may affect cardiac autonomic function; however, the limited findings in young adults with COVID-19 have been equivocal. Notably, symptomology and time since diagnosis appear to influence vascular health following COVID-19, but this has not been explored in the context of cardiac autonomic regulation. Therefore, we hypothesized that young adults who had persistent symptoms following COVID-19 would have lower heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) compared with those who had COVID-19 but were asymptomatic at testing and controls who never had COVID-19. Furthermore, we hypothesized that there would be relationships between cardiac autonomic function measures and time since diagnosis. We studied 27 adults who had COVID-19 and were either asymptomatic (ASYM; n = 15, 6 females); 21 ± 4 yr; 8.4 ± 4.0 wk from diagnosis) or symptomatic (SYM; n = 12, 9 females); 24 ± 3 yr; 12.3 ± 6.2 wk from diagnosis) at testing, and 20 adults who reported never having COVID-19 (24 ± 4 yr, 11 females). Heart rate and beat-to-beat blood pressure were continuously recorded during 5 min of rest to assess HRV and cardiac BRS. HRV [root mean square of successive differences between normal heartbeats (RMSSD); control, 73 ± 50 ms; ASYM, 71 ± 47 ms; and SYM, 84 ± 45 ms; P = 0.774] and cardiac BRS (overall gain; control, 22.3 ± 10.1 ms/mmHg; ASYM, 22.7 ± 12.2 ms/mmHg; and SYM, 24.3 ± 10.8 ms/mmHg; P = 0.871) were not different between groups. However, we found correlations with time since diagnosis for HRV (e.g., RMSSD, r = 0.460, P = 0.016) and cardiac BRS (overall gain, r = 0.470, P = 0.014). These data suggest a transient impact of COVID-19 on cardiac autonomic function that appears mild and unrelated to persistent symptoms in young adults.NEW & NOTEWORTHY The potential role of persistent COVID-19 symptoms on cardiac autonomic function in young adults was investigated. We observed no differences in heart rate variability or cardiac baroreflex sensitivity between controls who never had COVID-19 and those who had COVID-19, regardless of symptomology. However, there were significant relationships between measures of cardiac autonomic function and time since diagnosis, suggesting that COVID-19-related changes in cardiac autonomic function are transient in young, otherwise healthy adults.

Impact of COVID-19 on ambulatory blood pressure in young adults: a cross-sectional analysis investigating time since diagnosis.

Previous studies have reported detrimental effects of COVID-19 on the peripheral vasculature. However, reports on blood pressure (BP) are inconsistent, and measurements are made only in the laboratory setting. To date, no studies have measured ambulatory BP. In addition, in previous studies, time since COVID-19 diagnosis among participants varied across a wide range, potentially contributing to the inconsistent BP results. Thus, we aimed to perform a comprehensive assessment of BP and BP variability using ambulatory and laboratory (brachial and central) measurements in young adults who had COVID-19. We hypothesized that ambulatory BP would be elevated post-COVID-19 and that measures of BP would be inversely related with time since diagnosis. Twenty-eight young adults who had COVID-19 [11 ± 6 (range 3-22) wk since diagnosis] and 10 controls were studied. Ambulatory daytime, nighttime, and 24-h systolic BP, diastolic BP, and mean BP were not different between the control and COVID groups (e.g., daytime systolic BP: control, 122 ± 12 mmHg; COVID, 122 ± 10 mmHg; P = 0.937). Similar results were observed for laboratory BPs (all P > 0.05). However, ambulatory daytime, nighttime, and 24-h BPs as well as laboratory brachial BPs were inversely correlated with time since COVID-19 diagnosis (e.g., daytime systolic BP: r = -0.444; P = 0.044, nighttime systolic BP: r = -0.518; P = 0.016). Ambulatory and laboratory-measured BP variability were not different between groups nor correlated with time since diagnosis. Collectively, these data suggest that adverse effects of COVID-19 on BP in young adults are minimal and likely transient.NEW & NOTEWORTHY We report for the first time that ambulatory daytime, nighttime, and 24-h blood pressure (BP), as well as laboratory BP, were not different between control and COVID participants. However, a significant inverse relationship with time since COVID-19 diagnosis was found (i.e., greater BP with more recent infection). Ambulatory and laboratory BP variability were unaffected and not related with diagnosis time. These findings suggest that COVID-19 may exert only short-lasting effects on BP in young adults.

Role of Endothelin-1 Receptors in Limiting Leg Blood Flow and Glucose Uptake During Hyperinsulinemia in Type 2 Diabetes.

Skeletal muscle insulin resistance is a hallmark of individuals with type 2 diabetes mellitus (T2D). In healthy individuals insulin stimulates vasodilation, which is markedly blunted in T2D; however, the mechanism(s) remain incompletely understood. Investigations in rodents indicate augmented endothelin-1 (ET-1) action as a major contributor. Human studies have been limited to young obese participants and focused exclusively on the ET-1 A (ETA) receptor. Herein, we have hypothesized that ETA receptor antagonism would improve insulin-stimulated vasodilation and glucose uptake in T2D, with further improvements observed during concurrent ETA + ET-1 B (ETB) antagonism. Arterial pressure (arterial line), leg blood flow (LBF; Doppler), and leg glucose uptake (LGU) were measured at rest, during hyperinsulinemia alone, and hyperinsulinemia with (1) femoral artery infusion of BQ-123, the selective ETA receptor antagonist (n = 10 control, n = 9 T2D) and then (2) addition of BQ-788 (selective ETB antagonist) for blockade of ETA and ETB receptors (n = 7 each). The LBF responses to hyperinsulinemia alone tended to be lower in T2D (controls: ∆161 ±â€…160 mL/minute; T2D: ∆58 ±â€…43 mL/minute, P = .08). BQ-123 during hyperinsulinemia augmented LBF to a greater extent in T2D (% change: controls: 14 ±â€…23%; T2D: 38 ±â€…21%, P = .029). LGU following BQ-123 increased similarly between groups (P = .85). Concurrent ETA + ETB antagonism did not further increase LBF or LGU in either group. Collectively, these findings suggest that during hyperinsulinemia ETA receptor activation restrains vasodilation more in T2D than controls while limiting glucose uptake similarly in both groups, with no further effect of ETB receptors (NCT04907838).

Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19.

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, to our knowledge, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral [brachial artery flow-mediated dilation (FMD) and reactive hyperemia] and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 wk past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight subjects with COVID-19 were symptomatic (SYM) and eight were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared with ASYM (6.8 ± 0.9%; P = 0.007) and control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared with ASYM (64 ± 19 cm/s; P = 0.025) and control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macrovascular and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared with controls who never had COVID-19.NEW & NOTEWORTHY This study was the first to investigate the persistent effects of COVID-19 on vascular function in otherwise healthy young adults. We demonstrated that peripheral macrovascular and microvascular vasodilation was significantly blunted in young adults still symptomatic from COVID-19 beyond the acute phase (>4 wk from diagnosis), whereas those who become asymptomatic have similar vascular function compared with controls who never had COVID-19. In contrast, cerebral vascular function and central arterial stiffness were unaffected irrespective of COVID-19 symptomology.

Sympathetic transduction in humans: recent advances and methodological considerations.

Ever since their origin more than one half-century ago, microneurographic recordings of sympathetic nerve activity have significantly advanced our understanding of the generation and regulation of central sympathetic outflow in human health and disease. For example, it is now appreciated that a myriad of disease states exhibit chronic sympathetic overactivity, a significant predictor of cardiovascular morbidity and mortality. Although microneurographic recordings allow for the direct quantification of sympathetic outflow, they alone do not provide information with respect to the ensuing sympathetically mediated vasoconstriction and blood pressure (BP) response. Therefore, the study of vascular and/or BP responses to sympathetic outflow (i.e., sympathetic transduction) has now emerged as an area of growing interest within the field of neural cardiovascular control in human health and disease. To date, studies have primarily examined sympathetic transduction under two distinct paradigms: when reflexively evoking sympatho-excitation through the induction of a laboratory stressor (i.e., sympathetic transduction during stress) and/or following spontaneous bursts of sympathetic outflow occurring under resting conditions (i.e., sympathetic transduction at rest). The purpose of this brief review is to highlight how our physiological understanding of sympathetic transduction has been advanced by these studies and to evaluate the primary analytical techniques developed to study sympathetic transduction in humans. We also discuss the framework by which the assessment of sympathetic transduction during stress reflects a fundamentally different process relative to sympathetic transduction at rest and why findings from investigations using these different techniques should be interpreted as such and not necessarily be considered one and the same.

Attenuated Rapid-Onset Vasodilation to Forearm Muscle Contraction in Black Men.

PURPOSE: Non-Hispanic Black individuals have a blunted ability to vasodilate at rest compared with other racial groups. Limited studies have investigated blood flow responses to exercise in Black individuals. Recently, our laboratory demonstrated that Black men exhibit attenuated increases in forearm vascular conductance (FVC) during steady-state rhythmic handgrip. The mechanisms for this remain unknown. Herein, we used single muscle contractions, a modality that allows for assessment of rapid-onset vasodilation (ROV) independent of major elevations in shear stress, tissue metabolism, and systemic hemodynamics. METHODS: Ten young, healthy Black and White men performed single forearm contractions at 20%, 40%, and 60% maximal voluntary contraction (MVC). In addition, cuff inflations were performed on the forearm to examine the contribution of mechanical compression to ROV. Forearm blood flow (FBF; duplex Doppler ultrasound), heart rate (ECG), and mean arterial pressure (Finometer) were continuously measured. FVC was calculated as FBF/mean arterial pressure. RESULTS: Baseline FVC (White men vs Black men, 0.75 ± 0.11 vs 0.80 ± 0.09 mL·min-1·mm Hg-1; P = 0.73), FBF, and MVCs (White men vs Black men, 54 ± 2 vs 54 ± 2 kg; P = 0.95) were similar between the groups. After single contractions, both groups exhibited intensity-dependent FVC and FBF increases during ROV; however, these responses were attenuated in the Black group at all intensities (e.g., 60%MVC FVC: White men vs Black men, +371% ± 37% vs +220% ± 23% baseline; P = 0.001). FVC and FBF responses to cuff inflation alone were also attenuated in Black individuals (P < 0.001). CONCLUSIONS: Collectively, these data indicate that Black men have an overall blunted ability to rapidly vasodilate compared with young White men.

Functional sympatholysis is preserved in healthy young Black men during rhythmic handgrip exercise.

Black men have attenuated increases in forearm vascular conductance (FVC) and forearm blood flow (FBF) during moderate- and high-intensity rhythmic handgrip exercise compared with White men, but the underlying mechanisms are unclear. Here, we tested for the first time the hypothesis that functional sympatholysis (i.e., attenuation of sympathetic vasoconstriction in the exercising muscles) is impaired in Black men compared with White men. Thirteen White and 14 Black healthy young men were studied. FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; Finometer) were measured at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. FVC was calculated as FBF/MAP. Sympathetic activation was induced via lower body negative pressure (LBNP) at -20 Torr for 2 min at rest and from the 3rd to the 5th min of handgrip. Sympathetic vasoconstriction was assessed as percent reductions in FVC during LBNP. The groups presented similar resting FVC, FBF, and MAP. During LBNP at rest, reductions in FVC were not different between White (-35 ± 10%) and Black men (-32 ± 14%, P = 0.616), indicating similar reflex-induced sympathetic vasoconstriction. During handgrip exercise, there were minimal reductions in FVC with LBNP in either group (White: -1 ± 7%; Black: +1 ± 8%; P = 0.523), indicating functional sympatholysis in both groups. Thus, contrary to our hypothesis, our findings indicate a preserved functional sympatholysis in healthy young Black men compared with White men, suggesting that this mechanism does not appear to contribute to reduced exercise hyperemia during moderate-intensity rhythmic handgrip in this population.

Augmented resting beat-to-beat blood pressure variability in young, healthy, non-Hispanic black men.

NEW FINDINGS: What is the central question of this study? The prevalence of hypertension in black individuals exceeds that in other racial groups. Despite this well-known heightened risk, the underlying contributory factors remain incompletely understood. We hypothesized that young black men would exhibit augmented beat-to-beat blood pressure variability compared with white men and that black men would exhibit augmented total peripheral resistance variability. What is the main finding and its importance? We demonstrate that young, healthy black men exhibit greater resting beat-to-beat blood pressure variability compared with their white counterparts, which is accompanied by greater variability in total peripheral resistance. These swings in blood pressure over time might contribute to the enhanced cardiovascular risk profile in black individuals. ABSTRACT: The prevalence of hypertension in black (BL) individuals exceeds that in other racial groups. Recently, resting beat-to-beat blood pressure (BP) variability has been shown to predict cardiovascular risk and detect target organ damage better than ambulatory BP monitoring. Given the heightened risk in BL individuals, we hypothesized young BL men would exhibit augmented beat-to-beat BP variability compared with white (WH) men. Furthermore, given studies reporting reduced vasodilatation and augmented vasoconstriction in BL individuals, we hypothesized that BL men would exhibit augmented variability in total peripheral resistance (TPR). In 45 normotensive men (24 BL), beat-to-beat BP (Finometer) was measured during 10-20 min of quiet rest. Cardiac output and TPR were estimated (Modelflow method). Despite similar resting BP, BL men exhibited greater BP standard deviation (e.g. systolic BP SD; BL, 7.1 ± 2.2 mmHg; WH, 5.4 ± 1.5 mmHg; P = 0.006) compared with WH men, which was accompanied by a greater TPR SD (P = 0.003), but not cardiac output SD (P = 0.390). Other traditional measures of variability provided similar results. Histogram analysis indicated that BL men exhibited a greater percentage of cardiac cycles with BPs higher (> +10 mmHg higher) and lower (< -8 mmHg lower) than mean systolic BP compared with WH men (interaction, P < 0.001), which was accompanied by a greater percentage of cardiac cycles with high/low TPR (P < 0.001). In a subset of subjects (n = 30), reduced sympathetic baroreflex sensitivity was associated with augmented BP variability (r = -0.638, P < 0.001), whereas cardiac baroreflex sensitivity had no relationship (P = 0.447). Herein, we document an augmented beat-to-beat BP variability in young BL men, which coincided with fluctuations in vascular resistance and reduced sympathetic BRS.

Muscle pump-induced inhibition of sympathetic vasomotor outflow during low-intensity leg cycling is attenuated by muscle metaboreflex activation.

Muscle sympathetic nerve activity (MSNA) decreases during leg cycling at low intensity because of muscle pump-induced increases in venous return and loading of the cardiopulmonary baroreceptors. However, MSNA increases during leg cycling when exercise is above moderate intensity or for a long duration, suggesting that the sympathoinhibitory effect of the cardiopulmonary baroreflex can be overridden by a powerful sympathoexcitatory drive, such as the skeletal muscle metaboreflex. Therefore, we tested the hypothesis that high-intensity muscle metaboreflex activation attenuates muscle pump-induced inhibition of MSNA during leg cycling. MSNA (left radial nerve) was recorded during graded isolation of the muscle metaboreflex in the forearm with postexercise ischemia (PEI) after low (PEI-L)- and high (PEI-H)-intensity isometric handgrip exercise (20% and 40% maximum voluntary contraction, respectively). Leg cycling (15-20 W) was performed alone and during each PEI trial (PEI-L+Cycling, PEI-H+Cycling). Cycling alone induced a significant decrease in MSNA burst frequency (BF) and total activity (TA). MSNA BF and TA also decreased when cycling was performed during PEI-L. However, the magnitude of decrease in MSNA during PEI-L+Cycling [∆BF: -19 ± 2% (P < 0.001), ∆TA: -25 ± 4% (P < 0.001); mean ± SE] was less than that during cycling alone [∆BF: -39 ± 5% (P = 0.003), ∆TA: -45 ± 5% (P = 0.002)]. More importantly, MSNA did not decrease during cycling with PEI-H [∆BF: -1 ± 2% (P = 0.845), ∆TA: +2 ± 3% (P = 0.959)]. These results suggest that muscle pump-induced inhibition of sympathetic vasomotor outflow during low-intensity leg cycling is attenuated by muscle metaboreflex activation in an intensity-dependent manner.NEW & NOTEWORTHY There are no available data concerning the interaction between the sympathoinhibitory effect of muscle pump-induced cardiopulmonary baroreflex loading during leg cycling and the sympathoexcitatory influence of the muscle metaboreflex. In this study, muscle metaboreflex activation attenuated the inhibition of muscle sympathetic nerve activity (MSNA) during leg cycling. This may explain, in part, the response of MSNA to graded-intensity dynamic exercise in which low-intensity leg cycling inhibits MSNA whereas high-intensity exercise elicits graded sympathoexcitation.

Sympathetic Transduction in Type 2 Diabetes Mellitus.

Approximately 60% of patients with type 2 diabetes mellitus (T2D) develop hypertension. Recent work also indicates greater blood pressure (BP) excursions throughout the day in T2D. Collectively, these findings suggest altered BP control in T2D. Although muscle sympathetic nerve activity (MSNA) recordings in T2D have provided equivocal results, quantification of MSNA alone does not account for ensuing vasoconstriction and BP responses elicited by MSNA. Thus, we tested the hypothesis that patients with T2D exhibit enhanced sympathetic transduction to BP. MSNA (microneurography) and beat-to-beat BP (Finometer) were measured at rest in 21 T2D and 13 age-matched and body mass index-matched control subjects and, signal-averaging was performed to quantify the mean arterial pressure and total vascular conductance responses to spontaneous bursts of MSNA. The peak mean arterial pressure and total vascular conductance responses to spontaneous MSNA were similar between T2D and control (both P>0.05). However, further analysis, separating T2D into those taking statins (n=13, T2D +statin) and not taking statins (n=8, T2D -statin), indicated that T2D -statin patients (4.2±0.6 mm Hg) exhibited greater peak mean arterial pressure responses compared with both T2D +statin patients (2.5±0.3 mm Hg, P=0.01) and control (control: 2.8±0.3 mm Hg, P=0.02). Likewise, nadir total vascular conductance responses to spontaneous MSNA bursts were greater in T2D -statin patients (T2D -statin: -3.3±0.6 mL/(min·mm Hg), T2D +statin: -1.6±0.3 mL/(min·mm Hg), P=0.03; control -2.2±0.3 mL/(min·mm Hg), P=0.08). Notably, T2D +statin patients exhibited similar peak mean arterial pressure and total vascular conductance responses to MSNA compared with control. Collectively, these findings demonstrate, for the first time, that patients with T2D exhibit augmented sympathetic transduction and this effect seems to be offset by statin therapy.

Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.