Forearm Vascular Responses Research Articles

Sex differences in forearm blood flow and vascular conductance responses to rhythmic handgrip exercise in young, healthy Hispanic/Latino adults

Hispanic individuals represent the largest ethnic minority in the United States and are projected to make up one-third of the U.S. population by 2060. Compared to non-Hispanic White (NHW) individuals, Hispanic adults exhibit a significantly higher prevalence of type 2 diabetes (17.9% in Hispanic men vs. 11.5% in NHW men and 14.6% in Hispanic women compared to 7.7% in NHW women). Consequently, Hispanic adults also experience a higher prevalence of other microvascular complications such as neuropathy, retinopathy, and nephropathy leading to end stage renal disease. The underlying mechanisms for this disproportionately high incidence of cardiovascular complications in Hispanic population remains largely unexamined. Previous studies indicate that vascular alterations may manifest early on in life in populations with high cardiovascular disease risk. To date, no study has investigated the differences in vascular function between healthy Hispanic men and women during exercise. Therefore, we tested the hypothesis that Hispanic women (HW) would exhibit greater relative increases in forearm blood flow (FBF) and vascular conductance (FVC) during rhythmic handgrip exercise compared to age-matched Hispanic men (HM). FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in 20 young, healthy Hispanic individuals (9 men, 11 women) during rhythmic handgrip exercise performed at three workloads (15%, 30%, and 45% of maximal voluntary contraction (MVC)). FVC was calculated as FBF/MAP. Baseline MAP (HM: 84 ± 5, HW: 85 ± 6 mmHg; p = 0.68) were similar between groups while baseline FBF (HM: 79.23 ± 21.43 and HW: 50.17 ± 28.33 ml/min; mean ± SD, p =0.02); FVC (HM: 0.95 ± 0.27 and HW: 0.60 ± 0.36 ml/min/mmHg; p =0.03); and MVCs (HM: 73.63 ± 18.14 and HW: 52.20 ± 10.73 kg; p < 0.001) were different between Hispanic men and women. Both groups exhibited intensity-dependent increases in FBF and FVC, [(mixed-model two-way ANOVA; %Δ FBF: sex effect p = 0.094, intensity effect p < 0.001, interaction p = 0.247) and (%Δ FVC: sex effect p = 0.032, intensity effect p < 0.001, interaction p = 0.14)]. For example, in response to 45% rhythmic hand grip intensity, there were no differences between Hispanic men and women, %Δ FBF (HM: 465.57 ± 98, HW: 527.27 ± 153.20; p = 0.32) and %Δ FVC (HM: 385.22 ± 65.32, HW: 455.90 ± 132.98; p = 0.17). Change in MAP from baseline to 45% rhythmic handgrip was similar between both groups ( p = 0.67). These preliminary data suggest that Hispanic men and women have similar hyperemic responses to rhythmic handgrip exercise at increasing intensities. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The forearm vascular response to sympathetic activation is attenuated in female, but not male, participants following acute intermittent hypoxia.

Acute exposure to hypoxia promotes both an increase in sympathetic nervous system activity (SNA) and local vasodilation. In rodents, intermittent hypoxia (IH)-mediated increases in SNA are associated with an increase in blood pressure in males but not females; notably, the protective effect of female sex is lost following ovariectomy. These data suggest the vascular response to hypoxia and/or SNA following IH may be sex- and/or hormone specific-although mechanisms are unclear. We hypothesized that hypoxia-mediated vasodilation and SNA-mediated vasoconstriction would be unchanged following acute IH in male adults. We further hypothesized that hypoxic vasodilation would be augmented and SNA-mediated vasoconstriction would be attenuated in female adults following acute IH, with the greatest effect when endogenous estradiol was high. Twelve male (25 ± 1 yr) and 10 female (25 ± 1 yr) participants underwent 30 min of IH. Females were studied in a low (early follicular) and high (late follicular) estradiol state. Preceding and following IH, participants completed two trials [steady-state hypoxia and cold pressor test (CPT)], where forearm blood flow and blood pressure were measured and used to determine forearm vascular conductance (FVC). The FVC response to hypoxia (P = 0.67) and sympathetic activation (P = 0.73) were unchanged following IH in males. There was no effect of IH on hypoxic vasodilation in females, regardless of estradiol state (P = 0.75). In contrast, the vascular response to sympathetic activation was attenuated in females following IH (P = 0.02), independent of estradiol state (P = 0.65). Present data highlight sex-related differences in neurovascular responsiveness following acute IH.NEW & NOTEWORTHY We examined the effects of acute intermittent hypoxia (AIH) on the vascular response to sympathetic activation and acute hypoxia. Present findings show, despite no effect of AIH on the vascular response to hypoxia, the forearm vasoconstrictor response to acute sympathetic activation is attenuated in females following AIH, independent of estradiol state. These data provide mechanistic understanding of potential benefits of AIH, as well as the impact of biological sex.

Forearm vascular conductance responses to rhythmic handgrip in young African American compared with Caucasian American women

Non-Hispanic African American (AA) individuals have a disproportionately high prevalence, and mortality rate of cardiovascular disease (CVD) compared to other populations. Previous studies have demonstrated that even young, healthy AA individuals have blunted flow-mediated dilation, attenuated vasodilatory responses to pharmacological infusions and rhythmic handgrip exercise (RHG), as well as higher arterial stiffness and exaggerated peripheral vasoconstriction to isometric handgrip exercise and other non-exercise-stimuli compared to Caucasian-American (CA) individuals. These studies indicate that vascular alterations occur early on in life of AA individuals, potentially contributing to elevated risk of CVD in this racial group. However, these racial disparities in vascular function have almost exclusively been studied in men. Herein, we tested the hypothesis that, similar to young AA men, young AA women will exhibit an attenuated increase in forearm blood flow (FBF) and forearm vascular conductance (FVC) during rhythmic handgrip exercise (RHG) compared to age-matched CA women. Forearm blood flow (FBF; duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in young CA (n = 5) and AA (n = 5) women during rhythmic handgrip exercise performed at three workloads (15%, 30%, and 45% of maximal voluntary contraction (MVC)). FVC was calculated as FBF/MAP. Baseline FBF (CA: 66.0 ± 12.8 and AA: 61.6 ± 12.2 ml/min; mean ± SD, p = 0.30); FVC (CA: 0.8 ± 0.2 and AA: 0.7 ± 0.2 ml/min/mmHg; p = 0.16), MAP (CA: 82 ± 11 and AA: 88 ± 4 mmHg; p = 0.28), and MVCs (CA: 50 ± 4 and AA: 52 ± 5 kg; p = 0.35) were similar between the groups. Both groups exhibited intensity-dependent increases in FBF and FVC; however, contrary to our hypothesis, there were no race difference (mixed-model two-way ANOVA; FVC: race effect p = 0.18, intensity effect p < 0.0001, interaction p = 0.48). For instance, in response to RHG at 45%, CA had 384 ± 112% increase in FBF from baseline and AA had 499 ± 153% increase. Increase in FVC from baseline was 198 ± 76% for CA women and 314 ± 151% for AA women. MAP did not differ between the groups (e.g., ΔMAP at 45%; CA: 13 ± 11 vs AA: 9 ± 5, p = 0.41). These preliminary data suggest that the hyperemic response to rhythmic handgrip exercise in young African American women are similar to age-matched Caucasian-American women. Supported byKinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Forearm vascular conductance responses to rhythmic handgrip in young Hispanic American adults compared to Caucasian American adults

Hispanic American (HA) individuals have double the prevalence and earlier onset of Type 2 Diabetes (T2D) compared to Caucasian American (CA) individuals. The underlying mechanisms for this disproportionately high incidence of T2D in HA individuals remains unknown. Impaired vascular dysfunction is a well-known hallmark of T2D however, very few studies have investigated vascular function in HA population. Equivocal results have been reported regarding flow-mediated dilation (FMD), a measure of endothelium-mediated, nitric oxide-dependent vasodilation in response to a cuff inflation, in HA population. In addition, vascular responsiveness during exercise has not been investigated in this racial group. Previous studies have indicated that exercise at increasing workloads elicits progressive increases in shear stress causing intensity-dependent vasodilation, which is primarily mediated by NO. Therefore, we aim to extend the previous findings by evoking a stepwise increase in shear stress during three exercise workloads to investigate the vascular function in HA adults during exercise. We tested the hypothesis that HA individuals would exhibit an attenuated forearm blood flow (FBF) and forearm vascular conductance (FVC) compared to CA individuals during RHG (rhythmic handgrip exercise). Forearm blood flow (duplex Doppler ultrasound), heart rate (ECG) and mean arterial pressure (MAP; finger photoplethysmography) were measured in young, healthy CA (n = 17 (7M/10F)) as well as in young, healthy HA (n = 13 (7M/6F)) during three trials of RHG performed at 15%, 30%, and 45% of their maximum voluntary contraction (MVC). As studies have reported sex differences in vascular function in HA previously, data will be presented in different sexes(Mean±standard deviation). In men, baseline FBF (CA: 121.1±45.6, HA: 98.7±34.5, p=0.28), MAP (CA: 84±6, HA: 85±7, p=0.47), FVC (calculated as FBF/MAP, p=0.28), and MVCs (CA: 79±15, HA: 74±17, p=0.19) were similar between groups. Similarly, in women, baseline FBF (CA: CA: 67.8±22.6, HA: 67.3±5.2, p=0.98), MAP (CA: 84±9, HA: 82±6, p=0.64), FVC (p=0.95), and MVC (CA: 49±6, HA: 53±13, p=0.21) were not different between groups. In men, an intensity-dependent increase in FVC and FBF was observed, with no difference between the racial groups (e.g., %Δ FVC 45%MVC CA=417±296% vs. HA=367±84% in HA; race effect p=0.40, intensity effect p<0.01, interaction p=0.32). Increase in MAP was also not significant (e.g., ΔMAP 45%MVC CA=8±5, HA=11±7, p=0.50) In women, a similar intensity-dependent increase in FVC and FBF was observed (e.g., %Δ FVC 45%MVC: 455±164% in CA, 418±104% in HA; race effect p=0.48, intensity effect p<0.01, interaction p=0.92). Increase in MAP was also not significant. (e.g., ΔMAP 45%MVC CA=15±8, HA=12±8, p=0.41) These preliminary findings indicate that vascular function during rhythmic handgrip exercise is preserved in Hispanic men and women, compared to their white counterparts. Kinesiology and Health Education UT Austin Start-Up Account 19-2635-91 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Forearm vascular resistance responses to the Valsalva maneuver in healthy young and older adults.

Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. Healthy young (N = 36; 19 women; age 25.4 ± 4.6years) and older (N = 21; 12 women; age 62.4 ± 9.6years) adults performed a supine 40mmHg, 20s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP2A-1; r = 0.337; p = 0.0206). This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope.

FOREARM VASCULAR RESPONSES TO MENTAL STRESS AND DEVICE GUIDED BREATHING ASSOCIATE WITH PLASMA CONCENTRATIONS OF NORMETADRENALINES IN SUBJECTS WITH ESSENTIAL HYPERTENSION

Objective: Forearm vasodilator responses to mental stress (MS) are impaired in hypertensive compared to normotensive individuals by a mechanism that may relate to peripheral alpha-adrenergic activity antagonising that of neuronal nitric oxide. We investigated whether the response to MS may be dependent on the level of basal sympathetic activity as measured by plasma concentrations of normetadrenaline (NM) and how responses to slowing respiratory rate by device guided breathing (DGB, which reduces sympathetic activity) vary according to NM concentrations. Design and method: Subjects with essential hypertension were stratified according to concentrations of plasma NM into those with low NM (&lt; or = 500pmol/L) and high NM (&gt; or = to 750pmol/L). Forearm blood flow (FBF) was measured by venous occlusion plethysmography after 15 minutes of rest, during MS elicited by the Stroop word-colour test and during supervised DGB with breathing rate &lt; 10 breaths/minute. Results: Subjects with high NM (n = 30, 15 men) had greater body mass index than those with low NM (n = 30, 17 men): (mean ± SD) 31 ± 7 vs 27 ± 4 kg/m2 (P &lt; 0.05), but the two groups were similar with respect to age and brachial blood pressure (BP). During MS and DGB, changes in BP were similar in subjects in both low NM and high NM groups. MS increased FBF in both groups but the response in high NM was impaired as compared to subjects with low NM (34 ± 3 vs. 49 ± 3 %, P &lt; 0.05). DGB increased forearm vascular resistance to a lesser extent in subjects with high compared to low NM (1.21 ± 7.95 vs 5.50 ± 6.32 mmHg.100 mL/mL, P &lt; 0.05). Conclusions: These results are consistent with greater sympathetic vascular tone in patients with higher NM that antagonises forearm vascular responses to MS. Circulating concentrations of NM may identify subjects with impaired neuronal nitric oxide signalling.

Blunted blood pressure response to exercise and isolated muscle metaboreflex activation in patients with cirrhosis.

We sought to test the hypothesis that the cardiovascular responses to isolated muscle metaboreflex activation would be blunted in patients with cirrhosis. Eleven patients with cirrhosis and 15 healthy controls were evaluated. Blood pressure (BP; oscillometric method), contralateral forearm blood flow (FBF; venous occlusion plethysmography), and heart rate (HR; electrocardiogram) were measured during baseline, isometric handgrip at 30% of maximal voluntary contraction followed by postexercise ischemia (PEI). Forearm vascular conductance (FVC) was calculated as follows: (FBF/ mean BP) × 100. Changes in HR during handgrip were similar between groups but tended to be different during PEI (controls: Δ 0.5 ± 1.1 bpm vs. cirrhotic patients: Δ 3.6 ± 1.0 bpm, P = 0.057). Mean BP response to handgrip (controls: Δ 20.9 ± 2.7 mm Hg vs. cirrhotic patients: Δ 10.6 ± 1.5 mm Hg, P = 0.006) and PEI was attenuated in cirrhotic patients (controls: Δ 16.1 ± 1.9 mm Hg vs. cirrhotic patients: Δ 7.2 ± 1.4 mm Hg, P = 0.001). In contrast, FBF and FVC increased during handgrip and decreased during PEI similarly between groups. These results indicate that an abnormal muscle metaboreflex activation explained, at least partially, the blunted pressor response to exercise exhibited by cirrhotic patients. Novelty: Patients with cirrhosis present abnormal muscle metaboreflex activation. BP response was blunted but forearm vascular response was preserved. HR response was slightly elevated.

Inflammation in the subcutaneous adipose tissue does not attenuate endothelial function in subjects with diabetes mellitus and subjects with dyslipidaemia and hypertension: Across-sectional study.

SummaryBackgroundObesity is associated with low‐grade inflammation that may be related to vascular disease. We hypothesized that inflammation in the subcutaneous adipose tissue is associated with impaired endothelium‐dependent vasodilatation.MethodsWe assessed endothelial function by measuring forearm vascular response to acetylcholine and determined inflammation in subcutaneous fat biopsies in 2 groups of subjects; 15 patients with type 2 diabetes mellitus (T2DM) and 19 subjects with dyslipidaemia combined with hypertension (DcH). The adipose tissue inflammation score was based on adipocyte size, influx of macrophages and presence of crown‐like structures. We compared the vascular response to acetylcholine between subjects with and without adipose tissue inflammation.ResultsPatients with diabetes had clearly decreased vasodilatation compared to patients with DcH. In total, 23 of the 34 fulfilled the criteria of subcutaneous adipose tissue inflammation. However, there was no difference in vascular response to acetylcholine between the group with and without inflammation (changes in FBF from baseline 3.9 ± 0.8, 7.8 ± 1.0 and 13.6 ± 1.0 mL/dL/min compared to 4.3 ± 1.0, 7.9 ± 2.1 and 12.2 ± 2.4 mL/dL/min in response to acetylcholine 0.5, 2.0 and 8.0 μg/dL/min), nor was there a relationship between systemic hs‐CRP levels and endothelial function.ConclusionsWe confirm that subjects with T2DM have impaired endothelial function compared to age‐ and BMI‐matched subjects with DcH. However, endothelial function did not differ between participants with or without inflammation in the subcutaneous adipose tissue. These results suggest that fat tissue inflammation, at least in the subcutaneous compartment, does not affect vascular function.

Racial Differences in Forearm Vascular Conductance Response during Dynamic Handgrip Exercise

Healthy young African‐Americans (AA) present impaired vasodilator function compared to Caucasian‐Americans (CA), as indicated by reduced flow‐mediated dilation, and lower vasodilation during mental stress. Whether such impairments affect vascular responses to dynamic exercise is unclear. Previous studies used relatively low‐intensity dynamic handgrip exercise, which resulted in a tendency towards lower forearm vascular conductance (FVC) and brachial artery blood flow (BABF) responses in AA as exercise intensity increased from 10% to 20% maximal voluntary contraction (MVC). Therefore, we hypothesized that with higher intensities, AA would present an attenuated increase in FVC to dynamic exercise. To investigate this, healthy young CA men [N = 6; 23 ± 2 years (mean ± SEM)] and AA men (N = 6; 20 ± 2 years) performed 6 trials of dynamic handgrip exercise at absolute workloads of 4, 8, 12, 16, 20, and 24 kg, while BABF (duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photopletysmography) were continuously measured. FVC was calculated as: BABF/MAP. Each exercise trial lasted for 3 min with a duty cycle of 1‐s contraction/2‐s relaxation, with a minimum of 5‐min rest period between trials. Cadence was provided via metronome, with real‐time visual feedback of handgrip force. The groups had similar MVCs (CA: 56 ± 3 vs. AA: 53 ± 1 kg; P = 0.480), and the workloads used in the exercise trials represented an average of 7.4 ± 0.2%, 14.9 ± 0.4%, 22.3 ± 0.6%, 29.7 ± 0.8%, 37.1 ± 1.0%, and 44.6 ± 1.2% MVC. Both groups presented an intensity‐dependent increase in FVC. However, this FVC response was attenuated in the AA group (ANOVA interaction P = 0.046), with lower changes from BL at 8 kg (CA: +113 ± 10 vs. AA: +66 ± 10 mL min−1 100 mmHg−1; P = 0.025), 12 kg (CA: +152 ± 11 vs. AA: +89 ± 11 mL min−1 100 mmHg−1; P = 0.004), 16 kg (CA: +182 ± 14 vs. AA: +133 ± 14 mL min−1 100 mmHg−1; P = 0.020), and 24 kg (CA: +239 ± 21 vs. AA: +185 ± 21 mL min−1 100 mmHg−1; P = 0.011). Similarly, there was an intensity‐dependent increase in BABF in both groups, with a tendency of a lower response in the AA group (ANOVA group main‐effect P = 0.073). These preliminary findings suggest that, compared to CA, AA have an impaired vasodilator response to dynamic handgrip exercise.Support or Funding InformationSupported by UTA College of Nursing and Health InnovationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of hypervolemia by protein and glucose supplementation during aerobic training on thermal and arterial pressure regulations in hypertensive older men.

In Japan, the incidence of heat illness in older people has rapidly increased during midsummer in the last decade, and we suggested that whey-protein+carbohydrate supplementation during aerobic training would increased plasma volume (PV) to enhance thermoregulatory adaptation in older men (J Appl Physiol 107: 725-733, 2009); however, >60% of people age 65 and older suffer from hypertension, and the symptoms may be worsened by hypervolemia. To examine this, we randomly divided 21 older men (∼69 yr) with ∼160 mmHg for systolic and ∼90 mmHg for diastolic blood pressure at rest into two groups: Glc (n = 11) consuming glucose alone (25 g) and Pro-Glc (n = 10) consuming whey protein (10 g) + glucose (15 g), immediately after cycling exercise at 60-75% of peak aerobic capacity (V̇o2 peak) for 60 min/day, 3 days/wk, for 8 wk. Before and after training, we measured PV (dye dilution), baroreflex sensitivity (BRS) of heart rate (Valsalva maneuver), and carotid arterial compliance (CAC) from carotid arterial diameter (ultrasound imaging) responses to pulsatile arterial pressure change (photoplethysmography) at rest. Additionally, we measured esophageal temperature (Tes) and forearm skin blood flow (plethysmography) during exercise at 60% pretraining V̇o2 peak for 20 min in a warm environment. We found that the forearm skin vascular conductance response to increased Tes was enhanced in Pro-Glc with increased PV, but this was not found in Glc; however, despite the increased PV, arterial blood pressures rather decreased with increased CAC and BRS in Pro-Glc. Thus, the prescription was applicable to older men with hypertension to prevent heat illness during exercise.

Forehead versus forearm skin vascular responses at presyncope in humans.

Facial pallor is commonly observed at presyncope in humans, suggestive of reductions in facial skin blood flow (SkBF). Yet, cutaneous vasoconstriction is usually minimal at presyncope when measured at the forearm. We tested the hypothesis that reductions in forehead SkBF at presyncope are greater than in the forearm. Forehead and forearm SkBF (laser-Doppler) and blood pressure (Finometer or radial artery catheterization) were measured during lower body negative pressure (LBNP) to presyncope in 11 normothermic and 13 heat-stressed subjects (intestinal temperature increased ∼1.4°C). LBNP reduced mean arterial pressure from 91 ± 5 to 57 ± 7 mmHg during normothermia (P ≤ 0.001) and from 82 ± 5 to 57 ± 7 mmHg during heat stress (P ≤ 0.001). During normothermia, LBNP decreased forehead SkBF 55 ± 14% compared with 24 ± 11% at the forearm (P = 0.002), while during heat stress LBNP decreased forehead SkBF 39 ± 11% compared with 28 ± 8% in the forearm (P = 0.007). In both conditions, most (≥68%) of the decreases in SkBF were due to decreases in blood pressure. However, a greater contribution of actively mediated reductions in SkBF was observed at the forehead, relative to the forearm during normothermia (32 ± 13% vs. 11 ± 11%, P = 0.031) and heat stress (30 ± 13% vs. 10 ± 13%, P = 0.004). These data suggest that facial pallor at presyncope is due to a combination of passive decreases in forehead SkBF secondary to reductions in blood pressure and to active decreases in SkBF, the latter of which are relatively greater than in the forearm.

Forearm vascular responses to mental stress in healthy older adults.

Forearm vascular conductance (FVC) increases in response to mental stress (verbal mental arithmetic) in young people. However, the effect of healthy aging and mental stress on FVC is unknown. In this study, we tested the hypothesis that FVC and cutaneous vascular conductance (CVC) would be attenuated in older adults compared to young adults. In 13 young (27 ± 1 year) and 11 older (62 ± 1 year) subjects, we quantified heart rate (HR), mean arterial pressure (MAP), FVC (Doppler ultrasound), and CVC (laser Doppler flowmetry) in response to a 3‐min bout of mental stress in the supine posture. Changes from baseline were compared between groups and physiological variables were also correlated. Older adults had a blunted HR response to mental stress (Δ = 7 ± 2 vs. 14 ± 2 beats/min) but ΔMAP was comparable between groups (Δ = 11 ± 2 mmHg vs. 9 ± 1). During the third minute of mental stress, the %ΔFVC (−2 ± 5 vs. 31 ± 12%) and %ΔCVC (2 ± 6 vs. 31 ± 15%) were both impaired in older adults compared to young subjects. There was no relationship between ΔHR and %ΔCVC in either group, but there was a positive relationship between ΔHR and %ΔFVC in both young subjects (R = 0.610, P < 0.027) and older subjects (R = 0.615, P < 0.044), such that larger tachycardia was associated with higher forearm vasodilation. These data indicate that older adults have impaired forearm vasodilation in response to mental stress.

Exercise-Induced Muscle Vasodilatation and Treadmill Exercise Test Responses in Individuals without Overt Heart Disease

Background: The beneficial effects of exercise on cardiovascular health may be related to the improvement in several physiologic pathways, including peripheral vascular function. The aim of this study was to evaluate the relationship between cardiovascular responses during the treadmill exercise test and exercise-induced muscle vasodilatation in individuals without overt heart disease. Methods: The study included 796 asymptomatic subjects (431 females and 365 males) without overt heart disease. We evaluated the heart rate (chronotropic reserve and heart rate recovery), blood pressure (maximum systolic and diastolic blood pressure as well as systolic blood pressure recovery) and exercise capacity during symptom-limited treadmill exercise testing. Exercise-induced muscle vasodilatation was studied with venous occlusion plethysmography and estimated by forearm blood flow and vascular conductance responses during a 3-min handgrip maneuver. Results: Forearm blood flow increase during the handgrip exercise was positively associated with heart rate recovery during treadmill exercise testing (p < 0.001). Forearm vascular conductance increase during the handgrip exercise was inversely associated with exercise diastolic blood pressure during exercise treadmill testing (p = 0.038). No significant association was found between exercise capacity and exercise-induced muscle vasodilation. Conclusion: In a sample of individuals without overt heart disease, exercise-induced muscle vasodilatation was associated with heart rate and blood pressure responses during treadmill exercise testing, but was not associated with exercise capacity. These findings suggest that favorable hemodynamic and chronotropic responses are associated with better vasodilator capacity, but exercise capacity does not predict muscle vasodilatation.

Short-term folinic acid supplementation improves vascular reactivity in HIV-infected individuals: A randomized trial

ObjectiveHIV-infected individuals present a cluster of conditions that activate or injure the vascular endothelium. The administration of folates may exert beneficial effects on endothelial function in different populations at risk for cardiovascular disease. The aim of this study was to determine the effects of 4 wk of folinic acid supplementation on forearm vascular responses during reactive hyperemia in HIV-infected patients under highly active antiretroviral therapy. MethodsThis was a prospective, randomized, double-blind, placebo-controlled trial to compare the effects of 4 wk of daily ingestion of 5 mg of folinic acid (n = 15) or placebo (n = 15). Participants had to have been on antiretroviral therapy (ART) for at least 6 mo before enrollment, with undetectable viral load, and CD4 cell count >200 cells/mm3. Vascular function was evaluated with venous occlusion plethysmography at baseline and after 4 wk, for the determination of brachial artery reactive hyperemia, and after isosorbide dinitrate administration. ResultsThe groups were comparable. The mean age of patients was 45 y; there were eight women in each group. There was no difference regarding ART regimen. The supplementation of folinic acid produced a significant improvement in reactive hyperemia (from 14.9 to 21.2 mL•min•100 mL). The same was not observed in placebo group (from 15.3 to 14.6 mL•min•100 mL; group P, 0.017; time P < 0.001; interaction P < 0.001). Endothelium-independent responses remained unchanged. ConclusionsShort-term folinic acid supplementation improved vascular reactivity in HIV-infected individuals enrolled in the studied. As folate supplementation is safe and relatively inexpensive, long-term clinical trials should be conducted.

Total sleep deprivation alters cardiovascular reactivity to acute stressors in humans

Exaggerated cardiovascular reactivity to mental stress (MS) and cold pressor test (CPT) has been linked to increased risk of cardiovascular disease. Recent epidemiological studies identify sleep deprivation as an important risk factor for hypertension, yet the relations between sleep deprivation and cardiovascular reactivity remain equivocal. We hypothesized that 24-h total sleep deprivation (TSD) would augment cardiovascular reactivity to MS and CPT and blunt the MS-induced forearm vasodilation. Because the associations between TSD and hypertension appear to be stronger in women, a secondary aim was to probe for sex differences. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded during MS and CPT in 28 young, healthy subjects (14 men and 14 women) after normal sleep (NS) and 24-h TSD (randomized, crossover design). Forearm vascular conductance (FVC) was recorded during MS. MAP, FVC, and MSNA (n = 10) responses to MS were not different between NS and TSD (condition × time, P > 0.05). Likewise, MAP and MSNA (n = 6) responses to CPT were not different between NS and TSD (condition × time, P > 0.05). In contrast, increases in HR during both MS and CPT were augmented after TSD (condition × time, P ≤ 0.05), and these augmented HR responses persisted during both recoveries. When analyzed for sex differences, cardiovascular reactivity to MS and CPT was not different between sexes (condition × time × sex, P > 0.05). We conclude that TSD does not significantly alter MAP, MSNA, or forearm vascular responses to MS and CPT. The augmented tachycardia responses during and after both acute stressors provide new insight regarding the emerging links among sleep deprivation, stress, and cardiovascular risk.

Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins

ATP is an endothelium-dependent vasodilator, and findings regarding the underlying signaling mechanisms are equivocal. We sought to determine the independent and interactive roles of nitric oxide (NO) and vasodilating prostaglandins (PGs) in ATP-mediated vasodilation in young, healthy humans and determine whether any potential role was dependent on ATP dose or the timing of inhibition. In protocol 1 (n = 18), a dose-response curve to intrabrachial infusion of ATP was performed before and after both single and combined inhibition of NO synthase [N(G)-monomethyl-L-arginine (L-NMMA)] and cyclooxygenase (ketorolac). Forearm blood flow (FBF) was measured via venous occlusion plethysmography and forearm vascular conductance (FVC) was calculated. In this protocol, neither individual nor combined NO/PG inhibition had any effect on the vasodilatory response (P = 0.22-0.99). In protocol 2 (n = 16), we determined whether any possible contribution of both NO and PGs to ATP vasodilation was greater at low vs. high doses of ATP and whether inhibition during steady-state infusion of the respective dose of ATP impacted the dilation. FBF in this protocol was measured via Doppler ultrasound. In protocol 2, infusion of low (n = 8)- and high-dose (n = 8) ATP for 5 min evoked a significant increase in FVC above baseline (low = 198 ± 24%; high = 706 ± 79%). Infusion of L-NMMA and ketorolac together reduced steady-state FVC during both low- and high-dose ATP (P < 0.05), and in a subsequent trial with continuous NO/PG blockade, the vasodilator response from baseline to 5 min of steady-state infusion was similarly reduced for both low (ΔFVC = -31 ± 11%)- and high-dose ATP (ΔFVC -25 ± 11%; P = 0.70 low vs. high dose). Collectively, our findings indicate a potential modest role for NO and PGs in the vasodilatory response to exogenous ATP in the human forearm that does not appear to be dose or timing dependent; however, this is dependent on the method for assessing forearm vascular responses. Importantly, the majority of ATP-mediated vasodilation is independent of these putative endothelium-dependent pathways in humans.

Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.

Combined heat and mental stress alters neurovascular control in humans.

This study examined the effect of combined heat and mental stress on neurovascular control. We hypothesized that muscle sympathetic nerve activity (MSNA) and forearm vascular responses to mental stress would be augmented during heat stress. Thirteen subjects performed 5 min of mental stress during normothermia (Tcore; 37 ± 0°C) and heat stress (38 ± 0°C). Heart rate, mean arterial pressure (MAP), MSNA, forearm vascular conductance (FVC; venous occlusion plethysmography), and forearm skin vascular conductance (SkVCf; via laser-Doppler) were analyzed. Heat stress increased heart rate, MSNA, SkVCf, and FVC at rest but did not change MAP. Mental stress increased MSNA and MAP during both thermal conditions; however, the increase in MAP during heat stress was blunted, whereas the increase in MSNA was accentuated, compared with normothermia (time × condition; P < 0.05 for both). Mental stress decreased SkVCf during heat stress but not during normothermia (time × condition, P < 0.01). Mental stress elicited similar increases in heart rate and FVC during both conditions. In one subject combined heat and mental stress induced presyncope coupled with atypical blood pressure and cutaneous vascular responses. In conclusion, these findings indicate that mental stress elicits a blunted increase of MAP during heat stress, despite greater increases in total MSNA and cutaneous vasoconstriction. The neurovascular responses to combined heat and mental stress may be clinically relevant to individuals frequently exposed to mentally demanding tasks in hyperthermic environmental conditions (i.e., soldiers, firefighters, and athletes).

Prehypertension alters arterial pressure and forearm vascular responses to mental stress in humans

Neurovascular responses to mental stress (MS) have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA) and forearm vascular responses to MS are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would augment MS‐induced increases in MAP through altered MSNA and forearm vascular responses. We examined 11 PHT (systolic 120–139 or diastolic 80–89 mmHg; 21±1 yrs) and 11 NT (systolic &lt;120 and diastolic &lt;80 mmHg; 22±2 yrs) subjects during 5 min of mental arithmetic. MSNA, MAP, heart rate (HR), forearm vascular conductance (FVC) and resistance (FVR) were measured. Resting MSNA (8 ± 2 vs. 14 ± 5 bursts/min; P&lt;0.01) and MAP (80 ± 1 vs. 90 ± 1 mmHg; P&lt;0.001) were significantly higher in PHT subjects. PHT augmented MS‐induced increases in MAP (Δ10 ± 2 vs. Δ14 ± 4 mmHg; P&lt;0.05) and blunted MS‐induced decreases in FVR (Δ−16 ± 2 vs. Δ−8 ± 1 units; P&lt;0.01). PHT tended to blunt MS‐induced increases in FVC (Δ3 ± 1 vs. Δ2 ± 0 units; P=0.10). MS elicited similar increases in MSNA (Δ8 ± 2 vs. Δ8 ± 3 bursts/min) and HR (Δ23 ± 4 vs. Δ20 ± 4 beats/min) in NT and PHT subjects, respectively. We conclude that MS elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses. Supported by NIH.

Dissociation between reflex sympathetic and forearm vascular responses to lower body negative pressure in heart failure patients with coronary artery disease

Many heart failure (HF) patients exhibit paradoxical forearm vasodilation when central blood volume is reduced by lower body negative pressure (LBNP). We tested the hypothesis that this response results from reflex sympathetic withdrawal. We recorded simultaneously forearm blood flow, muscle sympathetic nerve activity (MSNA), and plasma norepinephrine (PNE) during four random applications of LBNP, -5, -10, -20, and -40 mmHg, in 12 men with HF (mean left ventricular ejection fraction = 24 + or - 2%) and 10 healthy, normal, age-matched men (N). Compared with N, MSNA burst frequency (P = 0.001) and PNE (P = 0.005) were significantly higher in the HF group, both at rest and during LBNP. As anticipated in N, LBNP -40 mmHg significantly increased MSNA (+14.2 + or - 2.5 bursts/min; P < 0.05) and PNE (+0.83 + or - 0.22 nmol/l; P < 0.05) and decreased forearm vascular conductance (FVC) (-11.7 + or - 3.2 ml.min(-1).mmHg(-1); P < 0.05). In the HF group, LBNP elicited similar increases in MSNA (+11.5 + or - 2.0; P < 0.05) and PNE (+0.85 + or - 0.12; P < 0.05), without affecting FVC significantly (-4.1 + or - 2.4; P = 0.01 vs. N, interaction P = 0.03). However, within the HF group, responses were bimodal: LBNP -40 mmHg increased MSNA in all subjects (P < 0.001), yet the six patients with nonischemic or dilated cardiomyopathy (DCM) exhibited significant vasoconstriction (decrease in FVC; P = 0.001), whereas the six patients with ischemic cardiomyopathy (ICM) exhibited significant vasodilation (increase in FVC; P < 0.02 vs. DCM and N; interaction P = 0.02). Cold pressor testing increased MSNA and decreased FVC in ICM (n = 4). Thus paradoxical forearm vasodilator responses to LBNP in HF are not mediated by reflex sympathetic withdrawal. ICM and DCM patients differ qualitatively in their vascular responses to hypotensive LBNP.