Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging.

Aging increases arterial stiffness and wave reflections that augment left ventricular wasted pressure effort (WPE). A single bout of exercise may be effective at acutely reducing WPE via reductions in arterial wave reflections. In young adults (YA) acute aerobic exercise decreases, whereas handgrip increases, wave reflections. Whether acute exercise mitigates or exacerbates WPE and arterial wave reflection in healthy aging warrants further examination. The purpose of this study was to determine if there are age-related differences in WPE and wave reflection during acute handgrip and aerobic exercise. When compared with baseline, WPE increased substantially in older adults (OA) during handgrip (5,219 ± 2,396 vs. 7,019 ± 2,888 mmHg·ms, P < 0.001). When compared with baseline, there was a robust reduction in WPE in OA during moderate-intensity aerobic exercise (5,428 ± 2,084 vs. 3,290 ± 1,537 mmHg·ms, P < 0.001), despite absolute WPE remaining higher in OA compared with YA during moderate-intensity aerobic exercise (OA 3,290 ± 1,537 vs. YA 1,188 ± 962 mmHg·ms, P < 0.001). There was no change in wave reflection timing indexed to ejection duration in OA during handgrip (40 ± 6 vs. 38 ± 4%, P = 0.41) or moderate-intensity aerobic exercise (40 ± 5 vs. 42 ± 8%, P = 0.99). Conversely, there was an earlier return of wave reflection in YA during handgrip (60 ± 11 vs. 52 ± 6%, P < 0.001) and moderate-intensity aerobic exercise (59 ± 7 vs. 51 ± 9%, P < 0.001). Changes in stroke volume were not different between groups during handgrip (P = 0.08) or aerobic exercise (P = 0.47). The greater increase in WPE during handgrip and decrease in WPE during aerobic exercise suggest that aortic hemodynamic responses to acute exercise are exaggerated with healthy aging without affecting stroke volume.NEW & NOTEWORTHY We demonstrated that acute aerobic exercise attenuated, whereas handgrip augmented, left ventricular hemodynamic load from wave reflections more in healthy older (OA) compared with young adults (YA) without altering stroke volume. These findings suggest an exaggerated aortic hemodynamic response to acute exercise perturbations with aging. They also highlight the importance of considering exercise modality when examining aortic hemodynamic responses to acute exercise in older adults.

Inverse salt sensitivity in normotensive adults: role of demographic factors.

BACKGROUND: Salt sensitivity and inverse salt sensitivity [ISS; a reduction in blood pressure (BP) on a high sodium diet] are each associated with increased incidence of hypertension. The purpose of this analysis was to determine the prevalence of ISS in normotensive adults and whether ISS is associated with any demographic characteristic(s). METHODS: Healthy normotensive, nonobese adults [ n  = 84; 43 women; age = 37 ±â€Š13 years; baseline mean arterial pressure (MAP) = 89 ±â€Š8 mmHg] participated in a controlled feeding study, consuming 7-day low-sodium (20 mmol sodium/day) and high-sodium (300 mmol sodium/day) diets. Twenty-four-hour ambulatory BP was assessed on the last day of each diet. ISS was defined as a reduction in 24-h MAP more than 5 mmHg, salt sensitivity as an increase in MAP more than 5 mmHg and salt resistance as a change in MAP between -5 and 5 mmHg from low sodium to high sodium. RESULTS: Using this cutoff, 10.7% were ISS, 76.2% salt resistant, and 13.1% salt sensitive. Prevalence of ISS was similar between sexes and age groups ( P  > 0.05). However, ISS was more prevalent in those with normal BMI (15.8% ISS) compared with those with overweight BMI (0% ISS; P  < 0.01). Interestingly, classification of participants using a salt sensitivity index (ΔMAP/Δ urinary sodium excretion) categorized 21.4% as ISS, 48.8% salt resistant, and 29.8% salt sensitive. CONCLUSION: Overall, we found that the prevalence of ISS was 10.7% (5 mmHg cutoff) or 21.4% (salt sensitivity index), and that ISS was associated with lower BMI. These results highlight the importance of future work to understand the mechanisms of ISS and to standardize salt sensitivity assessment.

Young, non-Hispanic Black men and women exhibit divergent peripheral and cerebral vascular reactivity.

NEW FINDINGS: What is the central question of the study? Do peripheral and cerebral vascular function differ between young non-Hispanic Black men and women? What is the main finding and its importance? The non-Hispanic Black women in this study presented greater peripheral conduit artery and cerebrovascular reactivity, yet similar peripheral microvascular function relative to the non-Hispanic Black men. These preliminary findings suggest that young Black women and men possess divergent vascular function, possibly contributing to the unique non-Hispanic Black sex differences in cardiovascular and cerebrovascular diseases. ABSTRACT: In the USA, cardiovascular and cerebrovascular diseases remain more prominent in the non-Hispanic Black (BL) population relative to other racial/ethnic groups. Typically, sex differences emerge in the manifestation of these diseases, though these differences may not fully materialize in the BL population. While numerous mechanisms are implicated, differences in vascular function likely contribute. Research has demonstrated blunted vasodilatation in several vascular regions in BL versus non-Hispanic White individuals, though much of this work did not assess sex differences. Therefore, this study aimed to ascertain if indices of vascular function are different between young BL women (BW) and men (BM). Eleven BW and 15 BM (22 (4) vs. 23 (3) years) participated in this study. Each participant underwent testing for brachial artery flow-mediated dilatation (FMD), post-occlusive reactive hyperaemia and cerebral vasomotor reactivity during rebreathing-induced hypercapnia. BW exhibited greater adjusted FMD than BM (P < 0.05 for all), but similar or lower reactive hyperaemia when assessed as blood velocity (P > 0.39 for all) or blood flow reactivity (P < 0.05 for all), respectively. Across a range of hypercapnia, BW had greater middle cerebral artery blood velocity and cerebrovascular conductance index than BM (P < 0.001 for both). These preliminary data suggest that young BW have greater vascular function relative to young BM, though this was inconsistent across different indices. These findings provide insight into the divergent epidemiological findings between BM and BW. Further research is needed to elucidate possible mechanisms and relate these physiological responses to epidemiological observations.

Global Reach 2018: Nitric oxide-mediated cutaneous vasodilation is reduced in chronic, but not acute, hypoxia independently of enzymatic superoxide formation.

We tested the hypotheses that 1) cutaneous microvascular function is impaired by acute normobaric and chronic hypobaric hypoxia and 2) that the superoxide free radical (via NADPH oxidase or xanthine oxidase) contributes to this impairment via nitric oxide (NO) scavenging. Local heating-induced cutaneous hyperemia (39 °C) was measured in the forearm of 11 male lowlanders at sea level (SL) and following 14-18 days at high altitude (HA; 4340 m in Cerro de Pasco, Peru), and compared to 11 highlanders residing permanently at this elevation. Cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure) was not different during 39 °C [control site: 73 (19) vs. 71 (18)%max; P = 0.68] between normoxia and acute normobaric hypoxia (FIO2 = 0.125; equivalent to HA), respectively. At HA, CVC was reduced during 39 °C in lowlanders compared to SL [control site: 54 (14) vs. 73 (19)%max; P < 0.01] and was lower in Andean highlanders compared to lowlanders at HA [control site: 50 (24) vs. 54 (14)%max; P = 0.02]. The NO contribution to vasodilation during 39 °C (i.e., effect of NO synthase inhibition) was reduced in lowlanders at HA compared to SL [control site: 41 (11) vs 49 (10)%max; P = 0.04] and in Andean highlanders compared to lowlanders at HA [control site: 32 (21) vs. 41 (11)%max; P = 0.01]. Intradermal administration (cutaneous microdialysis) of the superoxide mimetic Tempol, inhibition of xanthine oxidase (via allopurinol), or NADPH oxidase (via apocynin) had no influence on cutaneous endothelium-dependent dilation during any of the conditions (all main effects of drug P > 0.05). These results suggest that time at HA impairs NO-mediated cutaneous vasodilation independent of enzymatic superoxide formation.

Pulsatile load and wasted pressure effort are reduced following an acute bout of aerobic exercise.

Following aerobic exercise, sustained vasodilation and concomitant reductions in total peripheral resistance (TPR) result in a reduction in blood pressure that is maintained for two or more hours. However, the time course for postexercise changes in reflected wave amplitude and other indices of pulsatile load on the left ventricle have not been thoroughly described. Therefore, we tested the hypothesis that reflected wave amplitude is reduced beyond an hour after cycling at 60% V̇o2peak for 60 min. Aortic pressure waveforms were derived in 14 healthy adults (7 men, 7 women; 26 ± 3 yr) from radial pulse waves acquired via high-fidelity applanation tonometry at baseline and every 20 min for 120 min postexercise. Concurrently, left ventricle outflow velocities were acquired via Doppler echocardiography and pressure-flow analyses were performed. Aortic characteristic impedance (Zc), forward (Pf) and backward (Pb) pulse wave amplitude, reflected wave travel time (RWTT), and wasted pressure effort (WPE) were derived. Reductions in aortic blood pressure, Zc, Pf, and Pb were all sustained postexercise whereas increases in RWTT emerged from 60 to 100 min post exercise (all P < 0.05). WPE was reduced by ∼40% from 40 to 100 min post exercise (all P < 0.02). Stepwise multiple regression analysis revealed that the peak ΔWPE was associated with ΔRWTT (ß = -0.57, P = 0.003) and ΔPb (ß = 0.52, P = 0.006), but not Δcardiac output, ΔTPR, ΔZc, or ΔPf. These results suggest that changes in pulsatile hemodynamics are sustained for ≥100 min following moderate intensity aerobic exercise. Moreover, decreased and delayed reflected pressure waves are associated with decreased left ventricular wasted effort after exercise.NEW & NOTEWORTHY We demonstrate that pulsatile load on the left ventricle is diminished following 60 min of moderate intensity aerobic exercise. During recovery from exercise, the amplitude of the forward and backward traveling pressure waves are attenuated and the arrival of reflected waves is delayed. Thus, the work imposed upon the left ventricle by reflected pressure waves, wasted pressure effort, is decreased after exercise.

Blunted hyperemic response to mental stress in young, non-Hispanic black men is not impacted by acute dietary nitrate supplementation.

Non-Hispanic black individuals suffer from an elevated prevalence of hypertension and cardiovascular disease (CVD) relative to other populations. This elevated disease risk is, in large part, related to impaired vascular function, secondary to reduced nitric oxide (NO) bioavailability. Emerging evidence suggests that dietary nitrate supplementation improves several cardiovascular parameters, including vascular function, in part by increased NO bioavailability. However, whether these findings extend to a population of black individuals is unknown. This study tested the hypothesis that forearm blood flow responses in young, non-Hispanic, black (BL) men during a mental stress challenge would be blunted relative to young, non-Hispanic, white (WH) men. We further hypothesized that acute dietary nitrate supplementation would improve this response in BL men. This study comprised two parts (phase 1 and phase 2). Phase 1 investigated the difference in blood flow responses between young, BL, and WH men. In contrast, phase 2 investigated the effect of acute nitrate supplementation on the responses in a subset of the BL men from phase 1. Eleven (nine for phase 2) BL and eight WH men (23 ± 3 vs. 24 ± 4 yr, respectively) participated in this double-blind, placebo-controlled, randomized, crossover study. During each visit, hemodynamic responses during 3 min of mental stress were assessed in the brachial artery using duplex Doppler ultrasound. Phase 1 was completed in one visit, whereas phase 2 was completed over two visits separated by ∼1 wk. During phase 2, data were collected before and 2-h postconsumption of a beverage either high in nitrate content or nitrate depleted. In phase 1, peak forearm blood flow (FBF; P < 0.001), total FBF (P < 0.01), and forearm vascular conductance (FVC; P < 0.001) were blunted in the BL. During phase 2, prebeverage responses were similar to phase 1 and were unaffected following beverage consumption (P > 0.05 vs. prebeverage for all variables). These data indicate that young, BL men have blunted microvascular vasodilatory responses to acute mental stress, which may not be altered following acute nitrate supplementation.NEW & NOTEWORTHY This study tested the hypothesis that non-Hispanic black (BL) men have a blunted forearm hyperemic response to mental stress, which would be augmented following acute nitrate supplementation. The increase in forearm blood flow during mental stress was attenuated in BL men and was not impacted by nitrate supplementation. This supports findings of altered vascular function in this population. This is especially important as BL experience a higher prevalence of stress, which contributes to CVD risk.

Personalized physiologic flow waveforms improve wave reflection estimates compared to triangular flow waveforms in adults.

Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using pressure-flow relations, wave separation analysis can be used to decompose aortic pressure waveforms into forward- (Pf) and backward-traveling (Pb) components. Reflection magnitude, the ratio of pressure amplitudes (RM = Pb/Pf), is a predictor of heart failure and all-cause mortality. Aortic flow can be measured via Doppler echocardiography or estimated using a triangular flow waveform; however, the latter may underestimate the flow waveform convexity and overestimate Pb and RM. We sought to determine the accuracy of a personalized synthetic physiologic flow waveform, compared with triangular and measured flow waveforms, for estimating wave reflection indices in 49 healthy young (27 ± 6 yr) and 29 older adults [66 ± 6 yr; 20 healthy, 9 chronic kidney disease (CKD)]. Aortic pressure and measured flow waveforms were acquired via radial tonometry and echocardiography, respectively. Triangular and physiologic flow waveforms were constructed from aortic pressure waveforms. Compared with the measured flow waveform, the triangular waveform underestimated Pf in older, but not young, adults and overestimated Pb and RM in both groups. The physiologic waveform was equivalent to measured flow in deriving all wave reflection indices and yielded smaller mean absolute biases than the triangular waveform in all instances (P < 0.05). Lastly, central pulse pressure was associated with triangular, but not physiologic, mean biases for Pb and RM independent of age or central arterial stiffness (P < 0.05). These findings support the use of personalized physiologic flow waveforms as a more robust alternative to triangular flow waveforms when true flow cannot be measured.NEW & NOTEWORTHY We demonstrate that triangular flow waveforms overestimate wave reflection indices, particularly at higher central pulse pressures independent of age or carotid-femoral pulse wave velocity. In contrast, personalized physiologic flow waveforms provide equivalent wave reflection estimates as measured flow waveforms, thereby offering a more robust alternative to triangulation when aortic flow cannot be measured.

Mechanisms of Dietary Sodium-Induced Impairments in Endothelial Function and Potential Countermeasures.

Despite decades of efforts to reduce sodium intake, excess dietary sodium remains commonplace, and contributes to increased cardiovascular morbidity and mortality independent of its effects on blood pressure. An increasing amount of research suggests that high-sodium diets lead to reduced nitric oxide-mediated endothelial function, even in the absence of a change in blood pressure. As endothelial dysfunction is an early step in the progression of cardiovascular diseases, the endothelium presents a target for interventions aimed at reducing the impact of excess dietary sodium. In this review, we briefly define endothelial function and present the literature demonstrating that excess dietary sodium results in impaired endothelial function. We then discuss the mechanisms through which sodium impairs the endothelium, including increased reactive oxygen species, decreased intrinsic antioxidant defenses, endothelial cell stiffening, and damage to the endothelial glycocalyx. Finally, we present selected research findings suggesting that aerobic exercise or increased intake of dietary potassium may counteract the deleterious vascular effects of a high-sodium diet.

Apocynin and Tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans.

It has previously been shown that high dietary salt impairs vascular function independent of changes in blood pressure. Rodent studies suggest that NADPH-derived reactive oxygen species mediate the deleterious effect of high salt on the vasculature, and here we translate these findings to humans. Twenty-nine healthy adults (34 ± 2 yr) participated in a controlled feeding study. Participants completed 7 days of a low-sodium diet (LS; 20 mmol sodium/day) and 7 days of a high-sodium diet (HS; 300 mmol sodium/day) in random order. All participants were salt resistant, defined as a ≤5-mmHg change in 24-h mean BP determined while on the LS and HS diets. Laser Doppler flowmetry was used to assess cutaneous vasodilation in response to local heating (42°C) during local delivery of Ringer's (n = 29), 20 mM ascorbic acid (AA; n = 29), 10 µM Tempol (n = 22), and 100 µM apocynin (n = 22). Additionally, endothelial cells were obtained in a subset of participants from an antecubital vein and stained for nitrotyrosine (n = 14). Cutaneous vasodilation was attenuated by the HS diet compared with LS [LS 93.0 ± 2.2 vs. HS 86.8 ± 2.0 percentage of maximal cutaneous vascular conductance (%CVCmax); P < 0.05] and was restored by AA during the HS diet (AA 90.7 ± 1.2 %CVCmax; P < 0.05 vs. HS). Cutaneous vasodilation was also restored with the local infusion of both apocynin (P < 0.01) and Tempol (P < 0.05) on the HS diet. Nitrotyrosine expression was increased on the HS diet compared with LS (P < 0.05). These findings provide direct evidence of dietary sodium-induced endothelial cell oxidative stress and suggest that NADPH-derived reactive oxygen species contribute to sodium-induced declines in microvascular function. NEW & NOTEWORTHY High-sodium diets have deleterious effects on vascular function, likely mediating, in part, the increased cardiovascular risk associated with a high sodium intake. Local infusion of apocynin and Tempol improved microvascular function in salt-resistant adults on a high-salt diet, providing evidence that reactive oxygen species contribute to impairments in microvascular function from high salt. This study provides insight into the blood pressure-independent mechanisms by which dietary sodium impairs vascular function. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/dietary-sodium-oxidative-stress-and-microvascular-function/ .

Fast-food meal reduces peripheral artery endothelial function but not cerebral vascular hypercapnic reactivity in healthy young men.

Consumption of a representative fast-food meal (FFMeal) acutely impairs peripheral conduit artery vascular function; however, the effect on cerebral vascular function remains unknown. This study tested the hypothesis that a FFMeal would impair cerebral vascular function as indexed by an attenuated increase in cerebral vascular conductance (CVCI) in the middle cerebral artery (MCA) during a hypercapnic challenge. Ten healthy men (age: 24 ± 3 years, BMI: 24.3 ± 3.8 kg/m2 ) were studied under two conditions; a standardized FFMeal (990 kcals, 50% fat, 36% carbohydrate, 14% protein, and 2120 mg sodium) and a fasting control condition. Basal hemodynamics, cerebral vasomotor reactivity (CVMR), and brachial artery flow-mediated dilation (BA FMD) were completed after an overnight fast (Pre) and again 2 h and 4 h later both days. To assess CVMR, subjects rebreathed from a 5-L bag while MCA velocity (MCAVmean ) was measured using transcranial Doppler (TCD) ultrasound and converted into CVCI (MCAVmean /mean arterial pressure). Peripheral artery endothelial function was assessed via BA FMD following a standard 5-min occlusion protocol. As expected, BA FMD was reduced at 2 h (Pre: 6.6 ± 1.7% vs. 5.2 ± 1.8%, P = 0.01). However, despite significant impairment in BA FMD, neither peak CVCI%baseline nor CVMR was affected by the FFMeal (Control-Pre: 1.9 ± 1.1, 2 h: 2.1 ± 1.1, 4 h: 1.7 ± 1.1 ∆CVCI%·∆PET CO2-1 vs. FFMeal-Pre: 2.1 ± 1.1, 2 h: 2.2 ± 0.7, 4 h: 1.9 ± 0.9 ∆CVCI%·∆PET CO2-1 , time × condition P = 0.88). These results suggest that cerebral vascular reactivity to hypercapnia in healthy young men is not altered by an acute FFMeal.

Sex differences in the mechanisms mediating blunted cutaneous microvascular function in young black men and women.

The black population exhibits attenuated vasodilatory function across their lifespan, yet little is known regarding the mechanisms of this impairment. Recent evidence suggests a potential role for oxidative stress. Therefore, we tested the hypothesis that NADPH oxidase (NOX) and/or xanthine oxidase (XO) contribute to blunted nitric oxide (NO)-mediated cutaneous microvascular function in young black adults. In 30 white and black subjects (8 men and 7 women in each group), local heating was performed while NOX and XO were inhibited by apocynin and allopurinol, respectively, via intradermal microdialysis. The plateau in cutaneous vascular conductance (red blood cell flux/mean arterial pressure) during 39°C local heating at each site was compared with a control site perfused with lactated Ringer solution. Subsequent inhibition of NO synthase via Nω-nitro-l-arginine methyl ester allowed for quantification of the NO contribution to vasodilation during heating. Black individuals, relative to white individuals, had a blunted cutaneous vascular conductance plateau at the control site (45 ± 9 vs. 68 ± 13%max, P < 0.001) that was increased by both apocynin (61 ± 15%max, P < 0.001) and allopurinol (58 ± 17%max, P = 0.005). Black men and black women had similar responses to heating at the control site ( P = 0.99), yet apocynin and allopurinol increased this response only in black men (both P < 0.001 vs. control). The NO contribution was also increased via apocynin and allopurinol exclusively in black men. These findings suggest that cutaneous microvascular function is reduced because of NOX and XO activity in black men but not black women, identifying a novel sex difference in the mechanisms that contribute to blunted vascular responses in the black population. NEW & NOTEWORTHY We demonstrate that cutaneous microvascular responses to local heating are consistently reduced in otherwise healthy young black men and women relative to their white counterparts. Inhibition of NADPH oxidase and xanthine oxidase via apocynin and allopurinol, respectively, augments microvascular function in black men but not black women. These data reveal clear sex differences in the mechanisms underlying the racial disparity in cutaneous microvascular function.

Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2­boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 µl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ±â€¯12 vs. AA: 62 ±â€¯6 vs. %CVCmax; P < 0.001). This response was improved in AA at the l-arginine site (Control: 62 ±â€¯6 vs. l-arginine: 70 ±â€¯18%CVCmax; P < 0.05) but not in the arginase inhibited site (Control: 62 ±â€¯6 vs. Arginase inhibited: 62 ±â€¯13%CVCmax; P = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ±â€¯14 vs. AA: 44 ±â€¯6 Δ %CVCmax; P < 0.001). These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA.

Pronounced and sustained cutaneous vasoconstriction during and following cyrotherapy treatment: Role of neurotransmitters released from sympathetic nerves.

Cryotherapy is a therapeutic technique using ice or cold water applied to the skin to manage soft tissue trauma and injury. While beneficial, there are some potentially detrimental side effects, such as pronounced vasoconstriction and tissue ischemia that are sustained for hours post-treatment. This study tested the hypothesis that this vasoconstriction is mediated by 1) activation of post-synaptic α-adrenergic receptors and/or 2) activation of post-synaptic neuropeptide Y1 (NPY Y1) receptors. 8 subjects were fitted with a commercially available cryotherapy unit with a water perfused bladder on the lateral portion of the right calf. Participants were instrumented with four intradermal microdialysis probes beneath the bladder. The following conditions were applied at the four treatment sites: 1) control (Ringer solution), 2) combined post-synaptic ß-adrenergic receptors and neuropeptide (NPY) Y1 receptors blockade (P+B site), 3) combined post-synaptic α-adrenergic receptor, ß-adrenergic receptor, and NPY Y1 receptor blockade (Y+P+B site), and 4) blockade of pre-synaptic release of all neurotransmitters from the sympathetic nerves (BT site). Following thermoneutral baseline data collection, 1°C water was perfused through the bladder for 30min, followed by passive rewarming for 60min. Skin temperature (Tskin) fell from ~34°C to ~18.5°C during active cooling across all sites and there was no difference between sites (P>0.05 vs. control for each site). During passive rewarming Tskin rose to a similar degree in all sites (P>0.05 relative to the end of cooling). In the first 20min of cooling %CVC was reduced at all sites however, this response was blunted in the BT and the Y+P+B sites (P>0.05 for all comparisons). By the end of cooling the degree of vasoconstriction was similar between sites with the exception that the reduction in %CVC in the Y+B+P site was less relative to the reduction in the control site. %CVC was unchanged in any of the sites during passive rewarming such that each remained similar to values obtained at the end of active cooling. These findings indicate that the initial vasoconstriction (i.e. within the 1st 20min) that occurs during cryotherapy induced local cooling is achieved via activation of post-synaptic α-adrenergic receptors; whereas nonadrenergic mechanisms predominate as the duration of cooling continues. The sustained vasoconstriction that occurs following cessation of the cooling stimulus does not appear to be related to activation of post-synaptic α-adrenergic receptors or NPY Y1 receptor.

Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans.

NEW FINDINGS: What is the central question of this study? The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress. What is the main finding and its importance? The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population. ABSTRACT: African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10 mm ascorbic acid or 10 µm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) at a rate of 2.0 µl min-1 . Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax ) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23 ± 4 years old) subjects participated. During 39°C heating, the %CVCmax was lower in AA at the control (CA, 65 ± 20% versus AA, 47 ± 15%; P < 0.05) and ascorbic acid sites (CA, 73 ± 14% versus AA: 49 ± 17%; P < 0.01). At the tempol site, there were no differences between groups. This was followed by infusion of 10 mm l-NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with tempol. These data suggest that: (i) cutaneous vasodilatation in response to local heating is blunted in AA relative to CA; and (ii) elevated superoxide generation attenuates nitric oxide-mediated cutaneous vasodilatation in AA.

Exaggerated Vasoconstriction to Spontaneous Bursts of Muscle Sympathetic Nerve Activity in Healthy Young Black Men.

Blacks have the highest prevalence of hypertension, putting them at greater risk of cardiovascular disease and death. Previous studies have reported that, relative to whites, healthy black men have augmented pressor responses to sympathoexcitatory stressors. Although important, these studies do not inform about the resting state and the influence of spontaneous changes in resting muscle sympathetic nerve activity (MSNA). Likewise, little is known about the transduction of MSNA into a vascular response at rest on a beat-to-beat basis. Accordingly, we tested the hypothesis that relative to whites, blacks would exhibit greater vasoconstriction and pressor responses following spontaneous bursts of MSNA. Mean arterial pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest in 35 young healthy men (17 blacks and 18 whites). Signal averaging was used to characterize changes in leg vascular conductance, total vascular conductance, and mean arterial pressure following spontaneous MSNA bursts. Blacks demonstrated significantly greater decreases in leg vascular conductance (blacks: -15.0±1.0%; whites: -11.5±1.2%; P=0.042) and total vascular conductance (blacks: -8.6±0.9%; whites: -5.1±0.4%; P=0.001) following MSNA bursts, which resulted in greater mean arterial pressure increases (blacks: +5.2±0.6 mm Hg; whites: +3.9±0.3 mm Hg; P=0.04). These exaggerated responses in blacks compared with whites were present whether MSNA bursts occurred in isolation (singles) or in combination (multiples) and were graded with increases in burst height. Collectively, these findings suggest that healthy young black men exhibit augmented sympathetic vascular transduction at rest and provide novel insight into potential mechanism(s) by which this population may develop hypertension later in life.

Blunted cerebral vascular responsiveness to hypercapnia in obese individuals.

NEW FINDINGS: What is the central question of this study? Is there a difference in the cerebral vascular response to rebreathing-induced hypercapnia between obese and lean individuals? What is the main finding and its importance? The main finding is that obese individuals have an attenuated increase in cerebral vascular conductance during hypercapnia relative to lean individuals. This finding suggests cerebral vascular dysfunction in this population, which might contribute to the greater prevalence of cerebral vascular and neurocognitive disease in this population. Obesity increases the risk of cardiovascular disease by >45%. Furthermore, obesity is a contributory factor to cognitive impairment and Alzheimer's disease. The mechanisms accounting for this increased disease risk have not been clarified. This study tested the hypothesis that the total range of change (a) in cerebral blood velocity (CBV) and cerebral vascular conductance (CVCI) and the maximal (y0) CBV and CVCI achieved during rebreathing-induced hypercapnia would be attenuated in obese individuals. Sixteen lean and 15 obese individuals participated. The magnitude of rebreathing-induced hypercapnia was similar between groups (lean, ∆15 ± 3 mmHg versus obese, ∆15 ± 2 mmHg; P = 0.82). The total range of change in CBV during rebreathing (a; expressed as a percentage) was similar between groups (lean, 91 ± 24% versus obese, 76 ± 19%, P = 0.07), whereas the total range of change in CVCI during rebreathing (a; expressed as a percentage) was attenuated in the obese individuals (lean, 71 ± 20% versus obese, 51 ± 15%, P < 0.01). Likewise, the maximal increase in CBV during rebreathing (y0; expressed as a percentage) was similar between groups (lean, 189 ± 22% versus obese, 179 ± 20%, P = 0.20), whereas the maximal increase in CVCI during rebreathing (y0; expressed as a percentage) was attenuated in the obese individuals (lean, 172 ± 19% versus obese, 155 ± 17 %, P = 0.01). These data indicate that the cerebral vascular response to rebreathing-induced hypercapnia is attenuated in obese individuals. This impairment might be a factor contributing to the elevated cerebral vascular and neurocognitive disease risk in this population.

Influence of sex on microvascular and macrovascular responses to prolonged sitting.

Increased daily sitting time is associated with greater cardiovascular risk, and, on average, women are more sedentary than men. Recent reports have demonstrated that prolonged sitting reduces lower leg microvascular (reactive hyperemia) and macrovascular [flow-mediated dilation (FMD)] vasodilator function. However, these studies have predominately included men, and the effects of sitting in young women are largely unexplored. This becomes important given known sex differences in vascular function. Thus, herein, we assessed popliteal artery reactive hyperemia and FMD before and after a 3-h sitting period in healthy young women (n = 12) and men (n = 8). In addition, resting popliteal artery hemodynamics (duplex Doppler ultrasound) and calf circumference were measured before, during, and after sitting. Resting popliteal artery shear rate was reduced to a similar extent in both groups during the sitting period (women: -48.5 ± 8.4 s-1 and men: -52.9 ± 12.3 s-1, P = 0.45). This was accompanied by comparable increases in calf circumference in men and women (P = 0.37). After the sitting period, popliteal artery FMD was significantly reduced in men (PreSit: 5.5 ± 0.9% and PostSit: 1.6 ± 0.4%, P < 0.001) but not women (PreSit: 4.4 ± 0.6% and PostSit: 3.6 ± 0.6%, P = 0.29). In contrast, both groups demonstrated similar reductions in hyperemic blood flow area under the curve (women: -28,860 ± 5,742 arbitrary units and men: -28,691 ± 9,685 arbitrary units, P = 0.99), indicating impaired microvascular reactivity after sitting. These findings indicate that despite comparable reductions in shear rate during 3 h of uninterrupted sitting, macrovascular function appears protected in some young women but the response was variable, whereas men exhibited more consistent reductions in FMD. In contrast, the leg microvasculature is susceptible to similar sitting-induced impairments in men and women.NEW & NOTEWORTHY We demonstrate that leg macrovascular function was consistently reduced in young men but not young women after prolonged sitting. In contrast, both men and women exhibited similar reductions in leg microvascular reactivity after sitting. These data demonstrate, for the first time, sex differences in vascular responses to prolonged sitting.

Heart rate, blood pressure and repolarization effects of an energy drink as compared to coffee.

The goal of this study was to investigate the impact of energy drinks on haemodynamic and cardiac physiology. Comparisons were made to coffee as well as water consumption. In Protocol #1 the caffeine content was normalized to body weight to represent a controlled environment. Heart rate, blood pressure and cardiac QTc interval were assessed in 15 participants, on 4 days, prior to and for 6·5 h postconsumption of (i) energy drink (2 mg caffeine per kg body weight; low dose), (ii) energy drink (3 mg caffeine per kg body weight; medium dose), (iii) coffee (2 mg caffeine per kg body weight) and (iv) 250 ml water. In Protocol #2, the beverages were consumed in volumes that they are purchased to represent real-life conditions. The aforementioned measurements were repeated in 15 participants following (i) 1 16 oz can of energy drink (16 oz Monster), (ii) 1 24 oz can of energy drink (24 oz Monster), (iii) 1 packet of Keurig K-Cup Starbucks coffee (coffee) and (iv) 250 ml water. The order of the beverages was performed in a randomized double-blinded fashion. For both protocols, QTc interval, heart rate and systolic blood pressure were unchanged in any condition (P>0·05). Diastolic blood pressure and mean blood pressure were slightly elevated in Protocol #1 (P<0·05, main effect of time) with no difference between beverages (P<0·05, interaction of beverage × time); however, they were unaffected in Protocol #2 (P>0·05). These findings suggest that acute consumption of these commonly consumed beverages has no negative effect on cardiac QTc interval.

Sustained cutaneous vasoconstriction during and following cyrotherapy treatment: Role of oxidative stress and Rho kinase.

Cryotherapy is a therapeutic technique using ice or cold water applied to the skin to reduce bleeding, inflammation, pain, and swelling following soft tissue trauma and injury. While beneficial, there are some side effects such as pronounced vasoconstriction and tissue ischemia that are sustained for hours post-treatment. This study tested the hypothesis that this vasoconstriction is mediated by 1) the Rho-kinase pathway and/or 2) elevated oxidative stress. 9 subjects were fitted with a commercially available cryotherapy unit with a water perfused bladder on the lateral portion of the right calf. Participants were instrumented with three microdialysis probes underneath the bladder. One site received lactated ringers (control site), one received the Rho-Kinase inhibitor Fasudil, and one received Ascorbic Acid. Skin temperature (Tskin) and cutaneous vascular conductance (CVC) was measured at each site. Subjects had 1°C water perfused through the bladder for 30min, followed by passive rewarming for 90min. Tskin fell from ~34°C to ~18.0°C during active cooling across all sites and this response was similar for all sites (P>0.05 for all comparisons). During passive rewarming Tskin rose to a similar degree in all sites (P>0.05 relative to the end of cooling). %CVC was reduced during active cooling in all sites; however, the magnitude of this response was blunted in the Fasudil site relative to control (P<0.001 for all comparisons) and min 25 and 30 of cooling in the Ascorbic Acid site (P<0.05). During passive rewarming %CVC at the control and Ascorbic Acid sites did not change such that values were similar to the end of cooling (P>0.05 for each comparison). %CVC at the Fasudil site remained elevated during passive rewarming such that values were higher compared to the control and Ascorbic Acid sites throughout the 90min of passive rewarming (P<0.001 main effect of Fasudil). These findings indicate that the Rho-kinase pathway contributes to pronounced vasoconstriction during cryotherapy as well as the sustained vasoconstriction during the subsequent rewarming period post treatment.