Attenuated forearm vascular conductance responses to rhythmic handgrip in young African-American compared with Caucasian-American men

Abstract

Previous studies have demonstrated that African-American (AA) individuals have heightened vasoconstrictor and reduced vasodilator responses under resting conditions compared with Caucasian-American (CA) individuals. However, potential differences in vascular responses to exercise remain unclear. Therefore, we tested the hypothesis that, compared with CA subjects, AA subjects would present an attenuated increase in forearm vascular conductance (FVC) during rhythmic handgrip exercise. Forearm blood flow (FBF; duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in healthy young CA (n = 10) and AA (n = 10) men during six trials of rhythmic handgrip performed at workloads of 4, 8, 12, 16, 20, and 24 kg. FVC (calculated as FBF/MAP), FBF, and MAP were similar between groups at rest (FVC: 63 ± 7 ml·min⁻¹·100 mmHg⁻¹ in CA subjects vs. 62 ± 7 ml·min⁻¹·100 mmHg⁻¹ in AA subjects, P = 0.862). There was an intensity-dependent increase in FVC during exercise in both groups; however, AA subjects presented lower FVC (interaction P < 0.001) at 8-, 12-, 16-, 20-, and 24-kg workloads (e.g., 24 kg: 324 ± 20 ml·min⁻¹·100 mmHg⁻¹ in CA subjects vs. 241 ± 21 ml·min⁻¹·100 mmHg⁻¹ in AA subjects, P < 0.001). FBF responses to exercise were also lower in AA subjects (interaction P < 0.001), whereas MAP responses did not differ between groups (e.g., ∆MAP at 24 kg: +19 ± 2 mmHg in CA subjects vs. +19 ± 2 mmHg in AA subjects, interaction P = 0.950). These findings indicate lower hyperemic responses to rhythmic handgrip exercise in AA men compared with CA men.

NEW & NOTEWORTHY It is known that African-American individuals have heightened vasoconstriction and reduced vasodilation under resting conditions compared with Caucasian-American individuals. Here, we identified that the hyperemic response to moderate and high-intensity rhythmic handgrip exercise was lower in healthy young African-American men.

INTRODUCTION

A number of studies have demonstrated heightened vasoconstrictor and reduced vasodilator responses in African-American (AA) individuals compared with Caucasian-American (CA) individuals. For example, healthy young AA individuals present augmented vasoconstriction compared with CA individuals in response to spontaneous bursts of muscle sympathetic nerve activity at rest (35), during reflex-mediated sympathoexcitation (25, 31), and after intra-arterial infusion of the α₁-adrenergic agonist phenylephrine (31). Furthermore, AA individuals present attenuated vasodilator responses to mental stress (2) and after intra-arterial infusions of isoproterenol (β-adrenergic agonist) (19, 30, 31), sodium nitroprusside [endothelium-independent nitric oxide (NO)-mediated vasodilator] (2, 30), and methacholine (endothelium-dependent NO-mediated vasodilator) (30). These findings indicate a heightened vasoconstrictor and reduced vasodilator responsiveness in young AA compared with CA individuals. However, how these alterations in vascular responses may impact blood flow regulation during exercise remains unclear.

Although racial differences in vascular responses to exercise have been investigated, the number of studies performed is minimal and equivocal results have been reported. Specifically, one study showed no significant difference between CA and AA individuals in the elevation of forearm blood flow (FBF) during rhythmic handgrip (16), whereas another study reported a lower FBF response in AA individuals (15). The reason for these discrepancies is unclear. However, it should be noted that the exercise intensities used in these studies were relatively low [10−20% of maximal voluntary contraction (MVC)]. As such, it is unlikely that these low-intensity rhythmic handgrip protocols elicited significant elevations in sympathetic nerve activity (34) or substantial production of metabolic compounds (3). This is important because the hyperemic response to exercise is determined by a balance between an intensity-dependent increase in sympathetic activation (vasoconstriction) (12, 13) and the graded production of vasodilator and sympatholytic compounds in the contracting muscles (local vasodilation) (11, 23, 24); thus, potential alterations in these major regulatory factors would be more prominent during high-intensity exercise. Therefore, in the present study, we investigated racial differences in forearm vascular conductance (FVC) and FBF during graded intensities of rhythmic handgrip exercise at incremental absolute workloads of 4, 8, 12, 16, 20, and 24 kg. We hypothesized that AA individuals would present an attenuated increase in FVC during high-intensity rhythmic handgrip exercise.

In addition, a recent series of studies has promoted the use of rhythmic handgrip to assess vascular function, noting several advantages over traditional measures, such as flow-mediated dilation (FMD) (7, 8, 18, 36). For example, rhythmic handgrip allows the examination of vascular function in a more graded fashion with a range of exercise intensities. Rhythmic handgrip also appears to be more sensitive than FMD to detect vascular dysfunction (7, 8). Thus, we also used this approach, along with FMD measures, to further probe for potential vascular differences between AA and CA men.

METHODS

Study population.

Ten CA and ten AA healthy young men participated in the present study. Subjects were well matched for age and body mass index (Table 1). This study only included men to limit other factors that may also affect vascular responses to exercise, particularly at high absolute workloads, such as sex differences in MVC, forearm volume/mass, and the rate of fatigue development (17, 27, 32). Also, sex hormones are known to affect exercise responses (4, 5). All subjects were recreationally active, reporting an average frequency of (mean ± SE) 3 ± 0 exercise sessions/wk, with a duration of 60 ± 10 min/session, without any difference between the groups. Racial identification was self-reported, and subjects were included only if they identified themselves and both their biological parents as either CA or AA. All subjects provided written informed consent before participation. Participants were nonsmokers, not taking any prescription medications, multivitamins, or supplements, and free of any known cardiovascular, respiratory, neural, or metabolic disease determined via a medical and health history questionnaire. Study procedures conformed with the Declaration of Helsinki and were approved by the University of Texas at Arlington Institutional Review Board.

Table 1.

Subject characteristics

	Caucasian-American Subjects	African-American Subjects	P Value
Age, yr	22 ± 1	22 ± 1	0.749
Body mass index, kg/m2	24.2 ± 0.4	24.7 ± 1.2	0.717
Systolic blood pressure, mmHg	120 ± 2	117 ± 2	0.498
Diastolic blood pressure, mmHg	67 ± 2	65 ± 3	0.474
Forearm lean mass, kg	1.44 ± 0.04	1.55 ± 0.09	0.267
Maximal voluntary contraction, kg	53 ± 2	55 ± 2	0.614
Normalized flow-mediated dilation, %	5.6 ± 0.7	4.7 ± 0.8	0.366

Values are means ± SE.

Experimental measurements.

Heart rate (HR) was determined using a standard lead II electrocardiogram (model Q710, Quinton, Bothell, WA). Beat-to-beat blood pressure (BP) was measured using finger photoplethysmography (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) on the middle finger of the left hand, and the values were confirmed by brachial BP measurements obtained at rest by an automated sphygmomanometer (Welch Allyn, Skaneateles Falls, NY). Respiratory patterns were continuously monitored during the experiment with a pneumobelt placed around the abdomen (Pneumotrace II 1132, UFI, Morro Bay, CA).

Brachial artery diameter and blood velocity were measured in the right arm via duplex Doppler ultrasound (Logiq 7, GE Medical Systems, Milwaukee, WI). A linear array transducer (M12L) was placed ~5 cm proximal to the antecubital fossa, in a position that optimized visualization of arterial wall edges and sharpest blood velocity tracings. The skin was marked for probe placement to ensure all measurements were made in the same location. The artery was imaged at a frequency of 12−14 MHz. Pulse-wave velocity was measured at a frequency of 5 MHz, corrected to an insonation angle of 60°, with the sample volume encompassing the entire lumen without extending beyond the arterial wall edges.

Experimental protocol.

Each subject was familiarized with all experimental measurements and procedures in a preliminary visit before any data collection. Participants abstained from alcohol consumption and exercise for 24 h before any study visit. In addition, subjects were asked to abstain from caffeinated beverages for 12 h and fasted for a minimum of 2 h. Experiments were performed in a quiet, dimly lit room with ambient temperature between 21 and 22°C.

Participants were studied in the supine position, with the right arm extended and positioned on a table at the side of the bed. The arm position was supported by pads, and the hand was maintained at heart level. All handgrip trials were performed with the right hand. After instrumentation for cardiovascular measures, MVC was determined by asking the subject to squeeze a handgrip dynamometer (model 56380, Stoelting, Wood Dale, IL) to maximal effort three to six times. A minimum of 1 min was given between trials, and MVC was determined as the highest force achieved. Subjects then rested for a minimum of 10 min while beat-to-beat BP, HR, respiration, and FBF were continuously recorded. Next, participants performed six trials of rhythmic handgrip exercise at absolute workloads of 4, 8, 12, 16, 20, and 24 kg, separated by rest periods of at least 5 min to ensure that FBF had returned to baseline values. Each trial consisted of a 3-min resting baseline followed by 3 min of handgrip contractions at the specific workload with a duty cycle of 1-s contraction/2-s relaxation. The rhythm was dictated by an auditory signal of a metronome. The handgrip signal was recorded and displayed by an analog-to-digital data-acquisition system (Bridge Amp, AD Instruments, Sydney, NSW, Australia), which provided real-time visual feedback of handgrip force to the subject. When needed, subjects also received verbal feedback from the researchers. The rating of perceived exertion (RPE; Borg scale: 6–20) was asked at the end of each trial.

On a separate visit, endothelial function was assessed at rest, after an overnight fast, via FMD as previously described (1). Briefly, a cuff (SC10D, Hokanson, Bellevue, WA) was positioned ~3 cm distal to the antecubital fossa. Baseline diameter and velocity were recorded for 2 min using high-resolution Doppler ultrasound (Logiq P5, GE Medical Systems, Milwaukee, WI). The cuff was then inflated to 220 mmHg for 5 min (Rapid Cuff Inflation System, Hokanson). Diameter and velocity were recorded for 30 s before and for 3 min after cuff deflation. Positioning of the ultrasound probe was maintained during the entire recording with an articulated holder (Noga Engineering & Technology, Shlomi, Israel).

Data analysis.

Brachial artery diameter, blood velocity, and beat-to-beat BP were recorded using customized software interfaced with video output of the Doppler ultrasound machine (LabView, National Instruments; Austin, TX), as previously described (6, 14, 21, 29). Briefly, the BP signal was sampled at 1,000 Hz and embedded as a data stream into an AVI file containing video images output from the ultrasound. Additionally, HR, respiratory trace, and handgrip force were recorded by an analog-to-digital data-acquisition system (PowerLab 16/35, LabChart 8.1.8, AD Instruments) at a sample rate of 1,000 Hz. All blood flow measurements and analyses were performed by the same operator using customized edge detection programs (6, 14, 21, 29). FBF was calculated as follows: [π × (arterial diameter/2)² × blood velocity × 60]. Additionally, FVC was calculated as the ratio between FBF and time-aligned mean arterial pressure (MAP) from the Finometer. Shear rate was defined as follows: (8 × velocity/diameter). Linear regressions were performed on the individual data to analyze the relationship between changes in diameter and changes in shear rate across handgrip trials (33, 36). FBF and FVC responses to exercise were analyzed as absolute values and as values normalized to forearm lean mass, determined by dual energy X-ray absorptiometry (Prodigy, GE Healthcare, Milwaukee, WI). Responses to handgrip were also analyzed according to relative intensities. In the majority of subjects, we were able to identify trials that represented 15% (CA: 15.8 ± 0.4 vs. AA: 15.3 ± 0.3%), 30% (CA: 30.1 ± 0.7 vs. AA: 30.0 ± 0.5%), and 45% MVC (CA: 44.1 ± 0.7 vs. AA: 45.1 ± 0.9%) except for three subjects who did not have data representative of 45% MVC: two subjects (1 CA subject and 1 AA subject) had MVCs of 70 kg, with the highest absolute workload (24 kg) representing only 34% of their MVC, and the other subject who did not complete the 24-kg workload, with the 20-kg workload representing only 39% MVC.

FMD, expressed as the percent change in diameter, was calculated from three cardiac cycles averaged around the highest peak diameter using the following equation: FMD = (peak diameter – baseline diameter) × 100/baseline diameter. FMD percent change was normalized to shear rate area under curve from cuff release to peak diameter (20).

Statistical analysis.

Cardiovascular measures were averaged for 1 min at baseline and for the last 30 s of each exercise trial. There was no significant change in any baseline measures throughout the experiment; thus, an average of all baseline periods was used. One AA subject was unable to complete the 24-kg handgrip trial for 3 min. Therefore, responses to exercise trials were compared between groups using a mixed-effects model, with the fixed effects of group (CA, AA), workload (baseline, 4 kg, 8 kg, 12 kg, 16 kg, 20 kg, 24 kg), and interaction (group × workload). When a significant interaction was found, pairwise comparisons were made using Student’s t-test for independent samples. Subject characteristics, slopes, and R² values of the linear regressions were compared using Student’s t-test for independent samples. Significance levels was set for a P value of <0.05. Data are expressed as means ± SE unless stated otherwise, and statistical analyses were performed using SAS University Edition (SAS Institute, Cary, NC) and Statistica 8.0 (StatSoft, Tulsa, OK).

RESULTS

CA and AA groups had similar resting systolic and diastolic BP, forearm lean mass, and MVC (Table 1). Figure 1 shows absolute FVC, FBF, and MAP in each group at baseline and in response to each rhythmic handgrip trial. All measures were similar between CA and AA groups at baseline. Handgrip trials elicited increases in FVC in an intensity-dependent manner in both groups; however, compared with the CA group, the AA group presented lower FVC at workloads of 8, 12, 16, 20, and 24 kg (e.g., ∆FVC at 24 kg: +250 ± 15 ml·min⁻¹·100 mmHg⁻¹ in the CA group vs. +168 ± 18 ml·min⁻¹·100 mmHg⁻¹ in the AA group, interaction P < 0.001). Likewise, FBF during handgrip trials was lower in the AA group than in the CA group at 12, 16, 20, and 24 kg. In contrast, there was no group difference in MAP during any handgrip trial (e.g., ∆MAP at 24 kg: +19 ± 2 mmHg in the CA group vs. +19 ± 2 mmHg in the AA group, interaction P = 0.950).

Fig. 1.

Forearm vascular conductance, forearm blood flow, and mean arterial pressure in healthy young male Caucasian-American (CA) and African-American (AA) subjects at rest [baseline (BL)] and the end of rhythmic handgrip trials with incremental absolute workloads from 4 to 24 kg. *P < 0.05 for group comparison.

Table 2 shows brachial artery diameter, blood velocity, shear rate, HR, and RPE in each group at baseline and during each rhythmic handgrip trial. All measures were similar between CA and AA groups at baseline. Handgrip trials elicited intensity-dependent increases in all measures, with no difference between CA and AA groups. The individual linear regressions between changes in diameter per change in shear rate across all exercise workloads had similar slopes (CA: 0.00005 ± 0.00001 vs. AA: 0.00007 ± 0.00001, P = 0.301) and R² values (CA: 0.50 ± 0.10 vs. AA: 0.53 ± 0.10; P = 0.860). In agreement, FMD was similar between AA and CA groups (Table 1).

Table 2.

Cardiovascular variables and ratings of perceived exertion during baseline and at the end of each rhythmic handgrip trial

	Baseline	4 kg	8 kg	12 kg	16 kg	20 kg	24 kg	P Values
Brachial artery diameter, mm
CA	4.2 ± 0.2	4.2 ± 0.2	4.2 ± 0.2	4.2 ± 0.2	4.3 ± 0.1	4.4 ± 0.1	4.5 ± 0.2	Group: 0.079 Workload: <0.001 Interaction: 0.671
AA	3.8 ± 0.1	3.8 ± 0.1	3.8 ± 0.2	3.8 ± 0.1	4.0 ± 0.1	4.0 ± 0.1	4.1 ± 0.2
Brachial artery blood velocity, cm/s
CA	6.9 ± 0.6	15.0 ± 1.7	19.5 ± 1.3	24.4 ± 1.8	27.9 ± 1.7	34.4 ± 2.8	38.5 ± 3.0	Group: 0.230 Workload: <0.001 Interaction: 0.350
AA	8.0 ± 0.6	15.0 ± 1.5	17.2 ± 1.0	21.4 ± 1.6	24.5 ± 2.1	30.5 ± 3.2	34.2 ± 3.6
Shear rate, 1/s
CA	136 ± 15	299 ± 40	381 ± 36	475 ± 48	527 ± 44	638 ± 62	698 ± 63	Group: 0.959 Workload: <0.001 Interaction: 0.878
AA	174 ± 16	323 ± 43	366 ± 32	458 ± 50	509 ± 55	621 ± 79	678 ± 90
Heart rate, beats/min
CA	57 ± 2	63 ± 3	62 ± 3	63 ± 3	64 ± 2	71 ± 3	76 ± 4	Group: 0.539 Workload: <0.001 Interaction: 0.493
AA	59 ± 3	64 ± 3	66 ± 3	66 ± 3	70 ± 4	72 ± 4	74 ± 3
Rating of perceived exertion (Borg scale 6−20)
CA		8 ± 0	8 ± 0	10 ± 1	12 ± 1	13 ± 1	15 ± 1	Group: 0.805 Workload: <0.001 Interaction: 0.854
AA		8 ± 1	8 ± 1	10 ± 1	11 ± 1	13 ± 1	15 ± 1

Values are means ± SE. Baseline, average of all trials; CA, Caucasian-American; AA, African-American.

Figure 2 shows mean and individual absolute FVC, FBF, and MAP in each group at baseline and in response to rhythmic handgrip when expressed at the relative intensities of 15%, 30%, and 45% MVC. Compared with the CA group, the AA group presented lower FVC at all intensities (e.g., ∆FVC at 45% MVC: +252 ± 21 ml·min⁻¹·100 mmHg⁻¹ in the CA group vs. +164 ± 20 ml·min⁻¹·100 mmHg⁻¹ in the AA group, interaction P = 0.002). Likewise, FBF was lower in the AA group than in the CA group during handgrip trials at 30% and 45% MVC. In contrast, there was no group difference in MAP during any handgrip trial (e.g., ∆MAP at 45% MVC: +17 ± 3 mmHg in the CA group vs. +19 ± 2 mmHg in the AA group, interaction P = 0.853). All results were similar when FVC and FBF were adjusted to forearm lean mass (data not shown).

Fig. 2.

Forearm vascular conductance, forearm blood flow, and mean arterial pressure in healthy young male Caucasian-American (CA; mean: gray columns and individuals: white circles) and African-American (AA; mean: black columns and individuals: white triangles) subjects at rest [baseline (BL)] and the end of rhythmic handgrip trials from 15% to 45% MVC. *P < 0.05 for group comparison.

DISCUSSION

Our major novel finding is that healthy young AA men present an attenuated elevation in FVC and FBF during moderate- and high-intensity rhythmic handgrip exercise compared with healthy young CA men. These findings extend previous studies (15, 16) in which there were no significant differences in FVC and FBF between AA and CA individuals at lower handgrip intensities (10% and 20% MVC). Additionally, our study confirmed similar FBF responses between AA and CA individuals at low-intensity handgrip (15% MVC), which is within the range of handgrip intensities previously investigated (15, 16).

Exercise elicits both sympathetic vasoconstriction and local vasodilation in contracting muscle. A balance between these major mechanisms determines the magnitude of skeletal muscle hyperemia, and alterations leading to augmented vasoconstriction and/or blunted vasodilation would reduce muscle blood flow during exercise. Interestingly, exaggerated α₁-receptor-mediated vasoconstriction has been shown in AA individuals (31), associated with greater vasoconstriction in response to spontaneous bursts of muscle sympathetic nerve activity at rest (35) and during reflex-mediated sympathoexcitation (25, 31). Moreover, blunted endothelium-dependent (30) and endothelium-independent (2, 19, 30, 31) vasodilation have been shown in AA individuals. However, we found no differences in FMD or brachial artery vasodilation (∆diameter/∆shear rate) during exercise between groups, indicating that the AA individuals in our study did not have a generalized endothelial dysfunction or reduction in conduit artery vasodilation. Nevertheless, our results demonstrate consistently lower FVC and FBF responses to graded intensities of rhythmic handgrip in AA compared with CA men, most notably at moderate to high intensities.

Vasodilation during exercise is promoted by a number of factors (e.g., NO, prostaglandins, ATP, etc.) released from the contracting muscles, vascular endothelium, and erythrocytes (12). There is considerable redundancy between these factors (22, 28) as well as variable contributions at different exercise intensities (26, 36). In addition, local factors such as ATP and endothelium-derived hyperpolarization reduce the vasoconstrictor effect of norepinephrine on postjunctional α-adrenergic receptors in the contracting muscles (9, 10), thereby facilitating an increase in muscle blood flow in face of sympathetic activation during exercise (i.e., functional sympatholysis). The specific mechanisms leading to the lower blood flow response to exercise in AA individuals are unclear but may involve a combination of increased sympathetic vasoconstriction, reduced vasodilation, and/or reduced functional sympatholysis. Future studies investigating the regulation of blood flow during exercise in AA individuals are warranted.

Perspectives and Significance

A lower increase in blood flow to active skeletal muscles has the potential to impair exercise performance and increase BP responses, due to decreases in O₂ delivery and in the removal of metabolites that lead to fatigue. However, it is important to note that exercise performance of AA individuals did not appear to be impaired since, except for one AA subject, both groups completed the handgrip trials with the same absolute workloads and reported similar RPE values. Also, AA individuals did not present an exaggerated BP response to handgrip, which would be detrimental to cardiovascular health. Nevertheless, since muscle blood flow responses were reduced in AA individuals, it is likely that O₂ delivery was also reduced, and other mechanisms must be playing a compensatory role that kept exercise performance and BP responses similar to CA individuals. For example, muscle O₂ extraction may be higher in AA individuals, maintaining O₂ consumption at similar levels between groups. It is also possible that AA individuals had more efficient energy production at the mitochondrial level, reducing the O₂ demand for exercise. We would suggest that it is also unlikely that AA individuals relied more on anaerobic metabolism, because this would likely lead to greater metabolite production and exaggerated BP responses. Overall, further studies are needed to better understand the potential impact of lower blood flow responses on exercise performance and BP responses in AA individuals.

In conclusion, our findings demonstrate lower FVC and FBF responses to moderate and high-intensity rhythmic handgrip exercise healthy young AA men compared with healthy young CA men.

GRANTS

This work was supported by National Heart, Lung, and Blood Institute Grant HL-130906 (to D. M. Keller), American Heart Association Grant 20160072 (to P. J. Fadel), and the University of Texas at Arlington College of Nursing and Health Innovation. P. J. Fadel and T. C. Barbosa were supported by National Heart, Lung, and Blood Institute HL-127071 (to P. J. Fadel).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author(s).

AUTHOR CONTRIBUTIONS

T.C.B., J.K., R.M.B., and P.J.F. conceived and designed research; T.C.B., J.K., B.Y.S., and J.D.A. performed experiments; T.C.B. and J.K. analyzed data; T.C.B., J.K., D.M.K., R.M.B., and P.J.F. interpreted results of experiments; T.C.B. prepared figures; T.C.B., J.K., and P.J.F. drafted manuscript; T.C.B., J.K., B.Y.S., J.D.A., D.M.K., R.M.B., and P.J.F. edited and revised manuscript; T.C.B., J.K., B.Y.S., J.D.A., D.M.K., R.M.B., and P.J.F. approved final version of manuscript.