This study examined the effects of whole body heat stress on the sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors in healthy humans. Whole body heat stress accentuated the heart rate response, did not alter the muscle sympathetic nerve activity response, and lowered the pressure response to stimulation of muscle metaboreceptors. Moreover, whole body heat stress attenuated the blood pressure and sympathetic nerve responses to mechanoreceptor stimulation.
Keywords: autonomic, sympathetic, metaboreceptor, mechanoreceptor, hyperthermia
Abstract
The effects of whole body heat stress on sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors remains unclear. We examined the muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate in 14 young healthy subjects during fatiguing isometric handgrip exercise, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed under normothermic and whole body heat stress (increase internal temperature ~0.6°C via a heating suit) conditions. Heat stress increased the resting MSNA and heart rate. Heat stress did not alter the mean blood pressure (MAP), heart rate, and MSNA responses (i.e., changes) to fatiguing exercise. During PECO, whole body heat stress accentuated the heart rate response [change (Δ) of 5.8 ± 1.5 to Δ10.0 ± 2.1 beats/min, P = 0.03], did not alter the MSNA response (Δ16.4 ± 2.8 to Δ17.3 ± 3.8 bursts/min, P = 0.74), and lowered the MAP response (Δ20 ± 2 to Δ12 ± 1 mmHg, P < 0.001). Under normothermic conditions, passive stretch during PECO evoked significant increases in MAP and MSNA (both P < 0.001). Of note, heat stress prevented the MAP and MSNA responses to stretch during PECO (both P > 0.05). These data suggest that whole body heat stress attenuates the pressor response due to metaboreceptor stimulation, and the sympathetic nerve response due to mechanoreceptor stimulation.
NEW & NOTEWORTHY
This study examined the effects of whole body heat stress on the sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors in healthy humans. Whole body heat stress accentuated the heart rate response, did not alter the muscle sympathetic nerve activity response, and lowered the pressure response to stimulation of muscle metaboreceptors. Moreover, whole body heat stress attenuated the blood pressure and sympathetic nerve responses to mechanoreceptor stimulation.
whole body heat stress is a potent activator of the sympathetic nervous system (44). To maintain blood pressure in the face of large decreases in total vascular resistance associated with cutaneous vasodilation, cardiac output and regional vascular resistance of noncutaneous beds must increase. The increase in cardiac output is due mainly to an increase in heart rate, as stroke volume remains constant or rises by <10% in young, healthy heat-stressed subjects (19, 38, 46). The maintained stroke volume is associated with an increased ejection fraction and tissue Doppler determinants of systolic function (5, 9). Presumably these findings are due to a direct inotropic effect of heat stress (26, 45). This is accomplished via pronounced increases in muscle sympathetic nerve activity (MSNA), and vascular resistance of the splanchnic vascular beds (6, 38, 47).
It is well known that exercise evokes sympathetic nervous system activation (1, 34). This increase in sympathetic activity is due to central command and due to the exercise pressor reflex, a reflex engaged when chemically and mechanically sensitive muscle afferents within skeletal muscles are stimulated (34, 48). The combination of exercise and hyperthermia has been proposed as “probably the greatest stress ever imposed on the human cardiovascular system” (43). However, the effects of heat stress on the exercise pressor reflex have not been well studied.
Ray and Gracey (42) demonstrated that pronounced local heating of an isometric exercising muscle group (forearm) augmented the increase in MSNA during fatiguing exercise, whereas the MSNA response to the postexercise muscle ischemia was not altered. Thus, in that study (42), it was speculated that the elevated temperature might sensitize muscle mechanosensitive afferents. However, it is unclear if similar effects are observed in the setting of whole body heat stress conditions, where the increase in local muscle temperature can be less than the 4.5°C increase with local heating (42). Gao and colleagues (22), using a cat model, showed that sensitizing purinergic P2X receptors in hindlimb muscles under neutral or lower temperature accentuated the blood pressure response to passive stretch, whereas muscle heating attenuated this effect.
In one of our laboratory's previous reports (16), fatiguing isometric handgrip exercise was performed under whole body heat stress (increase internal temperature ~0.7°C). However, that study was designed to understand baroreflex function during heat stress, thus the roles of the muscle metaboreceptors and mechanoreceptors in the heat were not examined. Within this context, we sought to identify the effects of whole body heat stress on MSNA and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors. We hypothesized that MSNA and hemodynamic responses to stimulation of the muscle metaboreceptors and mechanoreceptors would be attenuated with whole body heat stress.
METHODS
Subjects.
Fourteen subjects (9 men, 5 women) participated in this study. The average age was 24 ± 1 yr, and all were of normal height (175 ± 3 cm) and weight (74 ± 3 kg). All subjects were nonhypertensive (supine blood pressures <140/90 mmHg). None were taking medications, and no subject had cardiovascular disease. Subjects refrained from caffeine, alcohol, and intense exercise 24 h before the study. The experimental protocol was approved by the Institutional Review Board of the Milton S. Hershey Medical Center and conformed with the Declaration of Helsinki. Each subject had the purposes and risks of the protocol explained to him or her before written, informed consent was obtained.
Measurements.
Internal temperature (Tcore) was measured from an ingestible telemetric temperature pill (HQ Technologies, Palmetto, FL) that was swallowed by volunteers ~1.5–2 h before data collection. Telemetry pill measurements correlate well with other Tcore measurements, such as esophageal temperature (40). Mean skin temperature (Tsk) was measured via the weighted average of six thermocouples attached to the skin on the chest, abdomen, upper back, lower back, thigh, and calf (21, 52). To indicate the increase in both Tsk and Tcore, mean body temperature (Tbody) was also calculated (0.9 × Tcore + 0.1 × Tsk) (56) and reported.
Each subject was dressed in a tube-lined suit that permitted control of Tsk by changing the temperature of the water-perfused suit. The suit covered the entire body surface, with the exception of both forearms and hands, the neck and head, the feet, and the lower leg from which nerve activity was recorded. Skin blood flow (SkBF) was indexed from dorsal forearm skin (nonexercising arm) using the mean values of 2 integrating flow probes of laser-Doppler flowmetry (MoorLab, Moor Instruments, Devon, UK). Cutaneous vascular conductance (CVC) was calculated from the ratio of the SkBF to mean arterial blood pressure (MAP). The final CVC was expressed as a percentage of the normothermic baseline. Forearm sweat rate was measured via capacitance hygrometry (Vaisala, Woburn, MA) using the ventilated capsule method (surface area = 2.0 cm2) adjacent to the laser-Doppler probe. The reported sweat rates are changes from the normothermic baseline reading. The areas from which SkBF and sweat rate were measured was not covered by the suit, and the local temperature of these areas was not controlled.
As described in our laboratory's previous reports, beat-by-beat blood pressure was recorded from a finger of the nonexercising arm (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) with resting values verified with an automated sphygmomanometer from the brachial artery (SureSigns VS3, Philips, Philip Medical System). Heart rate was monitored from the electrocardiogram (Cardicap/5, Datex-Ohmeda, GE Healthcare). Respiratory frequency was monitored using piezoelectric pneumography. Multifiber recordings of MSNA were obtained with a tungsten microelectrode inserted in the peroneal nerve. A reference electrode was placed subcutaneously 2–3 cm from the recording electrode. The signal was amplified, filtered with a bandwidth of 500–5,000 Hz, and integrated with a time constant of 0.1 s (Iowa Bioengineering, Iowa City, IA). The recording electrode was adjusted until a site was found in which muscle sympathetic bursts were clearly identified using previously established criteria (53). The nerve signal was routed to a computer screen and a loudspeaker for monitoring throughout the study.
Protocols.
The procedures were conducted with the subject in the supine position in a room with an ambient temperature of ~23°C. Before instrumentation, maximal force generated from a voluntary handgrip contraction (MVC) was determined upon repeated (i.e., ~3) isometric contractions from the nondominant arm using a handgrip dynamometer. The exercising forearm was not covered by the water-perfused suit. To ensure that the strength of the passive stretch was as vigorous as possible without evoking pain, the stretch strength for each subject was tested before the study. As described in our laboratory's previous reports (11, 14), a specifically designed brace with a joint at the wrist was used to support the subject’s forearm and hand. The hand was flexed in the dorsal direction (the extension of wrist, EOW), as the force was measured with a digital force gauge (IMADA, DPS-220, Northbrook, IL). During EOW, the position of the forearm and wrist remained fixed. The maximal force used to stretch the muscles without inducing pain was used for the stretch protocols before and after whole body heating. No subjects complained of pain with EOW.
Exercise paradigm.
After instrumentation, 6-min baseline measurements of heart rate, blood pressure, and MSNA were collected with the subject in the resting condition, while the tube-lined suit was perfused with 34°C water. Each subject then performed static isometric handgrip at 30% MVC to fatigue, followed by 4 min of postexercise circulatory occlusion (PECO), as shown in Fig. 1. A visual force indicator was used so that subjects could maintain the force necessary for 30% MVC. During grip, subjects were asked to report their perceived level of effort using the Borg scale of 6–20 (4). The determination of fatigue was based on the following: 1) the inability of the volunteer to maintain the desired force production; and 2) the assessment of the volunteers that the work was “extremely hard.” When a Borg scale of ~19 (extremely hard) was reported, a cuff on the upper arm was inflated to 250 mmHg before the subject stopped grip. The PECO was employed to isolate the metaboreflex. Passive stretch was employed to determine the contribution of mechanoreceptors under these conditions. EOW was performed for 1.5 min during the occlusion. To decrease any possible order effect, the EOW + PECO (1.5 min) and the PECO only (1.5 min) periods were in a random order in the last 3 min of the 4-min occlusion. Specifically, in 7 subjects, EOW started 1 min after cuff inflation (see Fig. 1). In other subjects, the EOW was performed during the last 1.5 min of the 4-min occlusion. The first minute's data from PECO were not included in all subjects. Subjects did not complain of any pain caused by EOW during PECO. Because our laboratory's previous study (14) showed that, under freely perfused conditions, passive stretch did not significantly alter MSNA, the EOW was not performed under freely perfused conditions in the present study.
Fig. 1.
Representative tracings of handgrip force, passive stretch force (EOW), heart rate (HR), muscle sympathetic nerve activity (MSNA), and arterial blood pressure (BP) in normothermic (top) and heat stress (bottom) conditions in one subject. bpm, Beats/min. In some subjects, the EOW started at 1 min from the onset of cuff inflation, as shown here, and the PECO data in these subjects were obtained in the 1.5-min window following the EOW. In other subjects, the EOW was performed during the last 1.5 min of the 4-min occlusion, and the PECO data in those subjects were obtained in the 1.5-min window before the EOW.
Whole body heating.
After data collection for the normothermic exercise trial, Tsk was increased to ~38°C by perfusing the tube-lined suit with 46°C water. After ~45–60 min, the heat stress increased Tcore by ~0.6°C. The temperature of the water was then reduced to 44–45°C in an attempt to reduce the rate of rise of Tcore during the exercise protocols in the heat-stressed condition. As heating was continued, 6-min measurements of heart rate, blood pressure, and MSNA were collected with the subject in the resting condition, and then the above exercise protocol was repeated.
Data analysis.
Data were sampled at 200 Hz via a data-acquisition system (MacLab, ADInstruments, Castle Hill, NSW, Australia). MSNA bursts were first identified in real time by visual inspection of the data, coupled with the burst sound from the audio amplifier. These bursts were further evaluated by a computer program that identified bursts based on fixed criteria, including an appropriate latency following the R wave of the electrocardiogram (11). Integrated MSNA in both thermal conditions was normalized by assigning a value of 100 to the mean amplitude of the largest 10% of the bursts during the 6-min normothermic baseline period (23). Normalization of the MSNA signal was performed to reduce variability between subjects attributed to factors, including needle placement. Total MSNA was identified from the burst area of the integrated neurogram that was evaluated on a beat-by-beat basis.
Stroke volume, cardiac output, and total peripheral resistance were estimated using the Beatscope software (Beatscope; Finapres Medical Systems). The same method has been documented to accurately track cardiac output during exercise (51). However, other reports (20, 27) suggest that, as compared with invasive measurements, the Finometer can be used to measure changes in cardiac output, whereas absolute measurements are associated with a higher level of variation. Thus, in the present report, stroke volume, cardiac output, and total peripheral resistance are reported as percent changes from the respective normothermic baseline values.
Responses were averaged during the 6-min period before exercise (baseline), the last minute of exercise, PECO alone (1.5 min), and EOW (1.5 min) during PECO. The change (i.e., Δ) in measured responses between the baseline and exercise periods was determined. Statistical analyses were performed using commercially available software (SigmaPlot 13.0, Systat Software). Baseline thermal and hemodynamic values between the normothermic and whole body heating trials were compared via paired t-tests. The effects of the whole body heating (factor 1: normothermic vs. heat stress) on the responses during the stages of the exercise paradigm (factor 2: resting baseline, handgrip, PECO only, and PECO + EOW) were evaluated via a two-way repeated-measures ANOVA, followed by multiple-comparison Tukey’s post hoc analyses, where appropriate. All values are reported as means ± SE. P values < 0.05 were considered statistically significant.
RESULTS
Whole body heating increased Tcore by 0.6 ± 0.1°C before the exercise trials in heat. The mean increase in Tbody during resting baseline in heat from normothermic Tbody was 0.9 ± 0.1°C. Whole body heating increased resting heart rate, cardiac output, MSNA, SkBF, CVC, and sweat rate; decreased diastolic blood pressure and total peripheral resistance; whereas systolic blood pressure, MAP, and stroke volume were not significantly changed (Table 1).
Table 1.
Thermal and hemodynamic responses to the heat stress before isometric handgrip exercise
| Normothermia | Heat Stress | |
|---|---|---|
| SBP, mmHg | 121 ± 2 | 122 ± 3 |
| DBP, mmHg | 61 ± 3 | 55 ± 1* |
| MAP, mmHg | 81 ± 1 | 78 ± 2 |
| Heart rate, beats/min | 60 ± 3 | 82 ± 3* |
| MSNA, bursts/min | 13 ± 2 | 26 ± 3* |
| MSNA, bursts/100 beats | 21 ± 3 | 32 ± 3* |
| SV, % | 100 | 100.3 ± 3.3 |
| CO, % | 100 | 133.6 ± 4.1* |
| TPR, % | 100 | 66.6 ± 5.0* |
| SkBF, %baseline | 100 | 696 ± 81* |
| CVC, %baseline | 100 | 730 ± 87* |
| Sweat rate, mg·cm−2·min−1 | 0.84 ± 0.12* | |
| Tcore, °C | 37.0 ± 0.1 | 37.6 ± 0.1* |
| Tsk, °C | 34.8 ± 0.1 | 38.3 ± 0.1* |
| Tbody, °C | 36.8 ± 0.1 | 37.7 ± 0.1* |
Values are means ± SE at baseline before exercise in both thermal conditions. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with an automated sphygmomanometer from the brachial artery. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were estimated using the Beatscope software with the Finometer device and were expressed as percentagge of the respective normothermic baseline. Skin blood flow (SkBF) and cutaneous vascular conductance (CVC) were expressed as percentage of the respective normothermic baseline. MSNA, muscle sympathetic nerve activity; Tcore, internal temperature; Tsk, mean skin temperature; Tbody, mean body temperature.
Significantly different from normothermia (P < 0.05).
Recordings of handgrip force, EOW force, heart rate, integrated MSNA, and blood pressure during the PECO and EOW in a representative subject are shown in Fig. 1. Tsk, Tcore, and Tbody did not change during the exercise trials, regardless of the thermal condition (Table 2). Handgrip exercise duration during heat stress was shorter than the duration during normothermia (226 ± 14 vs. 159 ± 12 s, P = 0.003). There was no difference in the end-exercise Borg scale values during normotheria (19.4 ± 0.2) and heat stress (19.6 ± 0.1, P = 0.43).
Table 2.
Temperatures, SkBF, and CVC during the exercise trials in normothermic and heat stress conditions
| Baseline | Handgrip | PECO | PECO + EOW | |
|---|---|---|---|---|
| Tsk, °C | ||||
| NT | 34.8 ± 0.1 | 35.1 ± 0.2 | 35.0 ± 0.1 | 35.0 ± 0.1 |
| HT | 38.3 ± 0.1* | 38.2 ± 0.1* | 38.2 ± 0.1* | 38.3 ± 0.1* |
| Tcore, °C | ||||
| NT | 37.0 ± 0.1 | 37.0 ± 0.1 | 37.0 ± 0.1 | 37.0 ± 0.1 |
| HT | 37.6 ± 0.1* | 37.6 ± 0.1* | 37.6 ± 0.1* | 37.6 ± 0.1* |
| Tbody, °C | ||||
| NT | 36.8 ± 0.1 | 36.8 ± 0.1 | 36.8 ± 0.1 | 36.8 ± 0.1 |
| HT | 37.7 ± 0.1* | 37.7 ± 0.1* | 37.7 ± 0.1* | 37.7 ± 0.1* |
| SkBF, % | ||||
| NT | 100 | 148 ± 10 | 120 ± 9 | 132 ± 10 |
| HT | 696 ± 81* | 824 ± 95*† | 815 ± 88*† | 835 ± 95*† |
| CVC, % | ||||
| NT | 100 | 111 ± 8 | 96 ± 7 | 105 ± 9 |
| HT | 730 ± 87* | 670 ± 83*† | 748 ± 89* | 751 ± 91* |
Values are means ± SE. Skin (Tsk), internal (Tcore), or mean body temperatures (Tbody) did not change within the exercise trials in normothermic (NT) or heat-stressed (HT) conditions. SkBF and CVC were expressed as percentage of the respective NT baseline.
Significantly different from the respective normothermic period (P < 0.05).
Significantly different from respective resting baseline (P < 0.05).
Isometric handgrip exercise, PECO, and the passive stretch during PECO evoked significant increases in MSNA, heart rate, MAP (Fig. 2), stroke volume, and cardiac output (Table 3) from the respective resting baseline in both thermal conditions. In the normothermic condition, CVC did not change with the exercise paradigm, whereas in the heat stress condition, CVC measured during the last minute of handgrip was lower than the resting baseline value (Table 2). The absolute heart rate and MSNA values during these stages of the heat stress trial were greater than those seen in the normothermic trial (Fig. 2). The absolute MAP and total peripheral resistance values during these stages of the exercise trial during heat stress were lower than those seen in the normothermic trial. The absolute cardiac output (Table 3), SkBF, and CVC (Table 2) during these stages of the exercise trial during heat stress were higher than those seen in the normothermic trial.
Fig. 2.
Absolute mean arterial pressure (MAP), HR, and MSNA burst rate and total activity, before exercise resting baseline (Rest) and during the last minute of the handgrip exercise (HG), PECO, and passive stretch during the occlusion (PECO + EOW) in normothermic (open bars) and heat stress (solid bars) conditions. MAP was calculated from the blood pressure waveform obtained from the Finometer. Values are means ± SE. *Significantly different from the respective normothermic period (P < 0.05). †Significantly different from the respective resting baseline before exercise (P < 0.05).
Table 3.
Hemodynamic variables during the exercise trials in normothermic and heat stress conditions
| Baseline | Handgrip | PECO | PECO + EOW | |
|---|---|---|---|---|
| SBP, mmHg | ||||
| NT | 122.4 ± 2.5 | 151.1 ± 4.1† | 147.4 ± 3.4† | 150.0 ± 3.5† |
| HT | 124.7 ± 3.3 | 151.4 ± 4.3† | 138.8 ± 3.6*† | 140.2 ± 3.5*† |
| DBP, mmHg | ||||
| NT | 59.9 ± 1.4 | 80.4 ± 2.3† | 75.0 ± 1.7† | 77.8 ± 1.7† |
| HT | 54.2 ± 1.3* | 74.0 ± 1.8*† | 64.0 ± 1.5*† | 65.5 ± 1.3*† |
| SV, % | ||||
| NT | 100 | 106.6 ± 3.4† | 118.3 ± 2.5† | 115.9 ± 2.8† |
| HT | 100.3 ± 3.3 | 103.0 ± 3.5 | 107.8 ± 3.7*† | 108.6 ± 3.7† |
| CO, % | ||||
| NT | 100 | 147.0 ± 5.0† | 127.8 ± 4.6† | 129.3 ± 5.6† |
| HT | 136.6 ± 4.1* | 178.3 ± 5.8†* | 165.2 ± 4.8†* | 167.0 ± 4.7†* |
| TPR, % | ||||
| NT | 100 | 91.3 ± 4.3† | 100.2 ± 3.6 | 104.0 ± 4.6 |
| HT | 66.6 ± 5.0* | 65.5 ± 4.8* | 63.0 ± 4.5* | 63.9 ± 4.5* |
Values are means ± SE. SBP, DBP, SV, CO, and TPR before exercise resting baseline and during the last minute of the handgrip exercise (handgrip), postexercise circulatory occlusion (PECO), and passive stretch during the occlusion (PECO + EOW) in normothermic (NT) and heat stress (HT) conditions are shown. SBP and DBP were obtained from the Finometer. SV, CO, and TPR were expressed as percentage of the respective normothermic baseline.
Significantly different from respective normothermic period (P < 0.05).
Significantly different from respective resting baseline (P < 0.05).
MSNA and hemodynamic responses to the fatiguing handgrip.
During the last minute of fatiguing handgrip, the increases from the prior exercise baseline for MAP (normothemia vs. heat stress: Δ24.9 ± 1.8 vs. Δ23.3 ± 1.5 mmHg, P = 0.52), heart rate (Δ23.3 ± 1.6 vs. Δ22.7 ± 2.6 beats/min, P = 0.75), and MSNA (burst rate: Δ17.8 ± 2.4 vs. Δ17.9 ± 3.3 bursts/min, P = 0.98; total activity: Δ445 ± 75 vs. Δ509 ± 108 units/min, P = 0.64) were not affected by the whole body heating. During the last minute of fatiguing handgrip, CVC decreased from the resting baseline in heat stress condition, but not in normothermic condition (Table 4).
Table 4.
Changes in SBP, DBP, SV, CO, SkBF, and CVC during the exercise paradigm
| Handgrip | PECO | PECO + EOW | |
|---|---|---|---|
| SBP, mmHg | |||
| NT | 28.7 ± 2.1 | 24.9 ± 2.1 | 27.5 ± 2.1‡ |
| HT | 26.7 ± 2.5 | 14.1 ± 1.7*† | 15.5 ± 1.4*† |
| DBP, mmHg | |||
| NT | 20.5 ± 1.7 | 15.1 ± 1.2† | 17.9 ± 1.4‡ |
| HT | 19.8 ± 1.6 | 9.8 ± 1.1*† | 11.3 ± 1.1*† |
| SkBF, % | |||
| NT | 48 ± 10 | 20 ± 9 | 32 ± 10 |
| HT | 127 ± 29* | 119 ± 19* | 139 ± 23* |
| CVC, % | |||
| NT | 11 ± 8 | −4 ± 7 | 5 ± 9 |
| HT | −59 ± 19* | 18 ± 17† | 21 ± 18† |
| SV, % | |||
| NT | 6.6 ± 3.4 | 18.3 ± 2.5† | 15.9 ± 2.8† |
| HT | 2.6 ± 1.9 | 7.5 ± 1.6*† | 8.3 ± 1.8*† |
| CO, % | |||
| NT | 47.0 ± 5.0 | 27.8 ± 4.6† | 29.3 ± 5.6† |
| HT | 41.7 ± 4.2 | 28.6 ± 3.2† | 30.4 ± 3.5† |
| TPR, % | |||
| NT | −8.7 ± 4.3 | 0.1 ± 3.6† | 4.0 ± 4.6† |
| HT | −1.0 ± 3.0* | −3.6 ± 2.9 | −2.6 ± 3.2 |
Values are means ± SE. Changes in SBP, DBP, SV, CO, SkBF, and CVC relative to prior exercise resting baseline during last minute of the handgrip, PECO only, and PECO + EOW, while subjects were in normothermic (NT) and heat stress (HT) conditions are shown. SkBF, CVC, SV, CO, and TPR were expressed as percentage of the respective normothermic baseline.
Significantly different from the respective normothermic period (P < 0.05).
Significantly different from respective handgrip period (P < 0.05).
Significantly different from respective PECO only period (P < 0.05).
MSNA and hemodynamic responses to metaboreceptor stimulation.
The open bars (normothermia) and the hatched bars (heat stress) in Fig. 3 show the responses to PECO (i.e., change from prior exercise baseline to PECO). Heat stress decreased the MAP response to PECO (Fig. 3, top left), and increased the heart rate response (Fig. 3, bottom left). However, the MSNA changes seen during PECO were not affected by heat stress (Fig. 3, top right and bottom right). A similar effect was seen during PECO + EOW (i.e., shaded bar vs. shaded hatched bar in Fig. 3). The increase in stroke volume during heat stress was significantly lower than that seen during normothermic conditions, while the increase in cardiac output during heat stress was not different from that seen during normothermic conditions (Table 4).
Fig. 3.
Increases in MAP, HR, and MSNA relative to resting baseline [i.e., change (Δ)] during postexercise circulatory occlusion (PECO) only and the passive stretch during the occlusion (PECO + EOW), while subjects were in normothermic and heat stress conditions. Open bars: PECO only under normothermia; shaded bars: PECO + EOW under normothermia; hatched bars: PECO only under heat stress; shaded hatched bars: PECO + EOW under heat stress. Values are means ± SE. *Significantly different from normothermia (P < 0.05). The passive stretch in normothermic condition evoked significant increases in MSNA and MAP (shaded vs. open bars), while these responses in heat stress were not significant (shaded hatched vs. hatched bars).
Effects of passive stretch.
During normothermia, the passive stretch during PECO (i.e., PECO + EOW) evoked significant increases in MSNA (P ≤ 0.001, in Fig. 3, top right and bottom right) and MAP (P < 0.001, Fig. 3, top left) from the PECO-only condition (i.e., open bar vs. shaded bar for PECO vs. PECO + EOW). After whole body heating, the passive stretch did not evoke significant increases in MSNA and MAP during PECO (i.e., hatched bar vs. shaded hatched bar in Fig. 3). No effect of passive stretch on stroke volume, cardiac output, or CVC was seen in either of the thermal conditions (Table 4).
DISCUSSION
Depending on the duration and intensity of the activity, exercise typically increases Tcore. A substantial literature exists regarding the mechanisms responsible for neural and associated cardiovascular responses to exercise (e.g., the roles of muscle metaboreceptors and mechanoreceptors). However, relatively little has been published examining how increases in temperature affect reflex responses to exercise. To that end, the present study was performed to identify whether neural and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors are modified if Tcore of the individual is modestly elevated before beginning exercise. The main findings of this study are that 1) whole body heat stress attenuates the blood pressure response seen when muscle metaboreceptors are selectively engaged; 2) whole body heat stress does not alter the MSNA response when muscle metaboreceptors are selectively engaged; and 3) whole body heat stress attenuates both MSNA and the blood pressure responses seen when muscle mechanoreceptors are stimulated in the presence of muscle metaboreceptors' engagement. These data provide evidence of an important effect of ambient heat on autonomic responses to exercise in humans.
Whole body heating raised the Tsk, Tcore, and the Tbody. Heat stress evoked increases in SkBF and CVC and a decrease in total peripheral resistance. With whole body heating, cardiac output was significantly increased, while stroke volume was not significantly altered. These observations are consistent with prior reports (19, 38, 46). Consistent with previous studies (16–18, 21, 28, 33), whole body heat stress evoked increases in resting heart rate and MSNA. Thus the absolute heart rate and MSNA values during each stage of the exercise paradigm were greater than those seen in the normothermic trial. Our main interest in this report was to examine the effects of whole body heat stress on the changes in MSNA and hemodynamic variables during each stage of the utilized exercise paradigm. We discuss these findings below.
Responses to fatiguing handgrip exercise.
Blood pressure, heart rate, and MSNA responses (i.e., changes) to fatiguing handgrip were not significantly different during the two thermal conditions. Consistent with the prior reports (7, 8, 37, 50), the CVC significantly decreased during the end of the handgrip exercise in heat stress in the present studies. Some prior reports (8, 50) suggested that both central command and the stimulation of muscle metaboreceptors could contribute to the CVC decrease during handgrip under the whole body heat stress condition. However, another report (37) suggested that the myogenic autoregulation may be an important contributor to the observed CVC decrease. Thus the reduction in CVC could be due to an increase in central command and the stimulation of muscle metaboreceptors or perhaps to a myogenic mechanism.
Although MSNA increased and CVC decreased, total peripheral resistance with handgrip during heat stress condition was not different from values seen during the resting baseline. Although the mechanism(s) is unclear, this observation was consistent with a prior report (3). In the present study, handgrip evoked a similar increase in cardiac output during the two thermal conditions. A prior report showed that the increases in both cardiac output and blood pressure evoked by 1-min handgrip exercise at 60% MVC was attenuated during heat stress condition compared with values seen during handgrip in normothermic condition (3). The differences in results could be due to differences in the exercise protocols used. We speculate that the maintained increase in cardiac output combined with the increased cutaneous vasoconstriction in heat stress contributed importantly to the maintained increase in blood pressure in the present study.
In the present study, the increases in blood pressure, heart rate, and MSNA during the fatiguing isometric exercise were not significantly different between the thermal conditions. The observations differ from results observed during local heating of exercising forearm muscles. Ray and colleagues (30, 31, 42) performed a series of studies evaluating MSNA, renal vasoconstriction, and hemodynamic responses to isometric handgrip exercise before and after local heating of exercising forearm muscles. In those studies, the increases in blood pressure and MSNA during isometric exercise were greater during local heating compared with the nonheated state. It should be noted that those studies were to examine the effects of local heating of muscles rather than the effects of whole body heating. In those studies, the local heating increased forearm muscle temperature from ~34 to 39°C. In the present study, the forearm was not covered by the heating suit. Thus the increase in the forearm muscle temperature before the exercise would be comparable to the increase in Tcore. We speculate that the difference in the exercising muscle temperature could be one of the possible causes for the differences in the MSNA and blood pressure responses.
In this report, we found that whole body heat stress did not significantly alter the increases in blood pressure, heart rate, and MSNA during the fatiguing isometric exercise. In a prior report (16), our laboratory found that the heart rate, MSNA, and blood pressure responses during the fatiguing isometric exercise were greater after whole body heating. We think that the differences in exercise paradigms are responsible for the differences in the results. First, it is recognized that the “central command” contributes to the exercise pressor reflex (54, 55). The handgrip was performed at 40% of MVC in the prior study and was at 30% MVC in the present study, respectively. Thus the contribution from “central command” to the exercise pressor reflex responses in the two studies could be different. Second, the assessment of “fatigue” was based on subjective reports (e.g., the Borg scale) of the volunteers in these two studies. Thus it is difficult to judge/compare the level of “fatigue” in two trials. This is a limitation of human studies. Moreover, totally different subjects were studied in the two studies, and this could have contributed to the different results in the two studies. Third, in the present study, handgrip duration during heat stress (one trial) was significantly shorter than the duration during normothermic condition (one trial). This is consistent with a previous report by Seals and Enoka (49), which demonstrated that a previous fatiguing contraction shortens the exercise duration of the subsequent fatiguing contraction performed under normothermic conditions. However, in that prior study (16), the handgrip duration during heat stress (mean value of 2 trials) was not significantly shorter than the duration during the normothermic conditions (mean value of 2–3 trials). The differences in the exercise paradigms could contribute to the different results.
Responses to muscle metaboreceptor stimulation.
In the present study, heat stress did not affect the MSNA responses during PECO. This suggests that this level of whole body stress does not alter the sympathetic efferent response as muscle metaboreceptors are stimulated.
Under the nonheating condition, it is known that the heart rate increase is limited during postexercise muscle ischemia (25, 39, 41). Some studies suggest that the limited heart rate response during metaboreceptor stimulation is due to an enhanced parasympathetic cardiac activity, although the sympathetic activity is increased (25, 39, 41). The present data show that the whole body heat stress accentuated the heart rate response during PECO (Fig. 3). This augmented heart rate response was not due to a further increase in temperatures during the exercise trial (see Table 2). We speculate that the augmented heart rate response is due to a decreased vagal tone by the whole body heat stress (10). The augmented heart rate response during PECO could also be due to elevated brain temperature by the whole body heat stress. This could affect the central command and/or the central activities of the exercise pressor reflex in the hypothalamus and/or ventrolateral medulla (2, 32).
During PECO, heat stress led to a decrease in absolute blood pressure (Table 3) and a decrease in the blood pressure response to PECO (Fig. 3). The mechanism(s) responsible for the observed attenuated pressor response is not known, but can be speculated upon. First, heat stress may impair neurovascular transduction. In rats, hyperthermia reduces blood pressure responses to α-adrenergic agonists (29, 35, 36). In humans, the magnitude of the increase in blood pressure seen with systemic infusions of the α1-agonist phenylephrine was noted to be attenuated during a heat stress intervention, similar to the one used in the present study (17). Thus impaired postsynaptic α-adrenergic-mediated vasoconstriction could contribute to the attenuated blood pressure response to a similar MSNA response by the muscle metaboreceptor stimulation. Second, under normothermic conditions, skin receives ~5–10% of the cardiac output; while upwards of 50% of the cardiac output is distributed to the skin during heat stress (45). Because such a large percentage of the cardiac output is redistributed to the skin (45), the percentage of the total cardiac output going to the skeletal muscles would decrease with heat stress. Under these conditions, increases in sympathetic vasoconstrictor activity directed to skeletal muscles with heat stress may not be sufficient to increase systemic arterial blood pressure to the same degree as seen under normothermic conditions. Third, no cutaneous vasoconstriction was observed during the PECO period in heat stress conditions, since the CVC during PECO was not lower than the values seen during resting baseline in heat stress. This observation is different from results noted in prior reports (8, 50), which suggested a cutaneous vasoconstriction during the postexercise occlusion in the heated individuals. The differences in the observations could be due to the differences in the protocols used. In those reports (8, 50), only 2-min postexercise occlusion was performed, and the 2-min data were reported. Importantly, the CVC in those reports tended to gradually increase during the 2-min postexercise occlusion. In the present study, 4-min postexercise occlusion was performed, and the data for PECO only and PECO + EOW was collected during the last 3 min. Whatever the responsible mechanisms, less cutaneous vasoconstriction during PECO could contribute to the attenuated blood pressure response. Fourth, although the increase in stroke volume during PECO in heat stress was lower than during PECO under normothermic conditions, the increase in heart rate was greater, and, in turn, the increases in cardiac output during PECO with heat stress were not different from the values seen during normothermic condition. Thus the attenuated pressure response during PECO was not due to an attenuated cardiac output response. Regardless of the mechanisms, during heat stress, heart rate responses are accentuated, whereas blood pressure responses are attenuated as muscle metaboreceptors are engaged.
Previous reports showed that local muscle heating did not alter the heart rate responses to the metaboreceptor stimulation (30, 31, 42). In those studies, local muscle heating either did not alter (42) or augment (31) the MSNA and blood pressure responses to the metaboreceptor stimulation. We speculate that the difference in the muscle temperatures and the differences between the local and the whole body heating could contribute to the different results between the previous and the present studies.
Responses to muscle mechanoreceptor stimulation.
Our laboratory has previously shown that passive muscle stretch during PECO increases in MSNA (14). The present results also show that passive muscle stretch during PECO evoked significant MSNA and MAP increases during normothermia. It should be noted that, even in normothermic conditions, the MSNA and MAP responses to EOW (i.e., EOW + PECO vs. PECO only) were modest compared with responses seen during handg rip (i.e., handgrip vs. resting baseline). This observation is consistent with prior findings (14, 15). The small response during EOW is likely due to the fact that only wrist and finger flexors were stretched during EOW, whereas handgrip exercise engaged wrist and arm flexors and extensors. Importantly, to avoid pain, the stretch force was less than during handgrip (see Fig. 1). Nevertheless, the prior and present data suggest that, in the normothermic condition, the stimulation of sensitized muscle mechanoreceptors evokes significant increases in MSNA and blood pressure. However, during heat stress, these effects of the passive stretch on MSNA were not seen. This finding provides additional evidence for the concept that whole body heat stress alters autonomic reflex responses to exercise.
For the attenuated responses to the stimulation of muscle mechanoreceptors during heat stress, several possible mechanisms can be speculated. First, the sensitivity of muscle mechanoreceptors may be decreased by the elevated muscle temperature. A previous study in cats (22) suggested that local heating attenuated the blood pressure response to passive stretch when purinergic P2X receptors were sensitized. Second, the observation could also be an effect of central origin. Specifically, it is possible that central responses to mechanoreceptor input might be reduced as brain temperature rises. Elevated temperatures could also alter central interaction between the inputs from mechanoreceptors (2, 32) and inputs from peripheral thermoreceptors (24).
The presented data suggest that whole body heat stress attenuates both MSNA and the blood pressure responses seen as muscle mechanoreceptors are engaged. Moreover, the blood pressure response seen as muscle metaboreceptors are engaged also attenuated during heat stress. Prolonged exercise not only increases metabolites, but also increases Tbody. The presented results suggest that, in addition to mechanical and metabolic changes within the exercising muscle, the Tbody can also importantly contribute to the autonomic and cardiovascular regulation during exercise. Elevated temperature may directly alter the sensitivity of muscle afferents (22). On the other hand, the increased blood flow by heating may induce changes in the chemical milieu of the interstitial space, which may also in turn alter the sensitivity of muscle afferents. Further studies are warranted.
Study limitations.
In the present study, heat stress was induced with the heating suit, which might result in a higher Tsk, a different distribution of blood flow and blood volume from those typically seen during exercise. This is a limitation of the experimental model. All exercise trials during heat stress were performed after the normothermic trial. Thus we cannot exclude an order effect. In three of our laboratory's previous reports (12, 13, 15), a similar exercise paradigm was performed twice under normothermic conditions. During the visits for the control studies (i.e., no drug was applied), the duration of the fatiguing handgrip in those studies also decreased in the second exercise trial in those studies (12, 13), while the MSNA and blood pressure responses to the handgrip were similar during the two trials. The MAP responses (changes) to PECO in the second exercise trial were not lower than those seen in the first trial. The passive stretch during PECO evoked significant MSNA and MAP responses in both trials in those studies (12, 13, 15). Thus, it is unlikely that the effects noted in the present study were due to the order of the trials.
In conclusion, the present data show that the moderate whole body heat stress (i.e., ~0.6°C increase in Tcore) does not alter the muscle sympathetic efferent response to muscle metaboreceptor stimulation; however, the systemic blood pressure responses are attenuated while the heart rate responses are accentuated. Whole body heat stress attenuated the sympathetic efferent and the blood pressure response to muscle mechanoreceptor stimulation. These observations suggest an interaction between heat stress and exercise on cardiovascular responses.
GRANTS
This work was supported by American Heart Association Grant 15GRNT24480051 (J. Cui), and National Institutes of Health Grants P01-HL-096570 (L. I. Sinoway) and UL1TR000127 (L. I. Sinoway).
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
AUTHOR CONTRIBUTIONS
J.C. and L.I.S. conception and design of research; J.C. and C.A.B. performed experiments; J.C. and C.A.B. analyzed data; J.C. and L.I.S. interpreted results of experiments; J.C. prepared figures; J.C. drafted manuscript; J.C. and L.I.S. edited and revised manuscript; J.C., C.A.B., and L.I.S. approved final version of manuscript.
ACKNOWLEDGMENTS
We express appreciation to the subjects for willingness to participate in this protocol. We are grateful to Jennifer L. Stoner for secretarial help in preparing this manuscript.
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