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Rapid regulation of arterial blood pressure on a beat-by-beat basis occurs primarily via arterial baroreflex control of cardiac output (CO) via rapid changes in heart rate (HR). Previous studies have shown that changes in HR do not always cause changes in CO, because stroke volume may vary. Whether these relationships are altered in hypertension is unknown. Using the spontaneous baroreflex sensitivity (SBRS) approach, we investigated whether baroreflex control of HR and CO were impaired after the induction of hypertension in conscious, chronically instrumented canines at rest, during mild exercise, and during exercise with metaboreflex activation (induced via reductions in hindlimb blood flow) both before and after induction of hypertension (induced via a modified Goldblatt approach—unilateral reduction in renal blood flow to ∼30% of control values until systolic pressure ≥ 140 mmHg and a diastolic pressure ≥ 90 mmHg for >30 days). After induction of hypertension, SBRS control of both HR and CO was reduced in all settings. In control, only about 50% of SBRS changes in HR caused changes in CO. This pattern was sustained in hypertension. Thus, in hypertension, the reduced SBRS in the control of HR caused reduced SBRS control of CO and this likely contributes to the increased incidence of orthostatic hypotension seen in hypertensive patients.

The purpose of the present study was to test our hypothesis that unloading the carotid baroreceptors alters the threshold and gain of the muscle metaboreflex in humans. Ten healthy subjects performed a static handgrip exercise at 50% of maximum voluntary contraction. Contraction was sustained for 15, 30, 45, and 60 s and was followed by 3 min of forearm circulatory arrest, during which forearm muscular pH is known to decrease linearly with increasing contraction time. The carotid baroreceptors were unloaded by applying 0.1-Hz sinusoidal neck pressure (oscillating from +15 to +50 mmHg) during ischemia. We estimated the threshold and gain of the muscle metaboreflex by analyzing the relationship between the cardiovascular responses during ischemia and the amount of work done during the exercise. In the condition with unloading of the carotid baroreceptors, the muscle metaboreflex thresholds for mean arterial blood pressure (MAP) and total vascular resistance (TVR) corresponded to significantly lower work levels than the control condition (threshold for MAP: 795 ± 102 vs. 662 ± 208 mmHg and threshold for TVR: 818 ± 213 vs. 572 ± 292 kg·s, P < 0.05), but the gains did not differ between the two conditions (gain for MAP: 4.9 ± 1.7 vs. 4.4 ± 1.6 mmHg·kg·s−1·100 and gain for TVR: 1.3 ± 0.8 vs. 1.3 ± 0.7 mmHg·l−1·min−1·kg·s−1·100). We conclude that the carotid baroreflex modifies the muscle metaboreflex threshold in humans. Our results suggest the carotid baroreflex brakes the muscle metaboreflex, thereby inhibiting muscle metaboreflex-mediated pressor and vasoconstriction responses. NEW & NOTEWORTHY We found that unloading the carotid baroreceptors shifts the pressor threshold of the muscle metaboreflex toward lower metabolic stimulation levels in humans. This finding indicates that, in the normal loading state, the carotid baroreflex inhibits the muscle metaboreflex pressor response by shifting the reflex threshold to higher metabolic stimulation levels.

We examined whether the sustained activation of metaboreceptor in forearm during cycling exercise can modulate sweating and cutaneous vasodilation. On separate days, 12 young participants performed a 1.5-min isometric handgrip exercise at 40% maximal voluntary contraction followed by 1) 9-min forearm ischemia (Occlusion, to activate metaboreceptor) or 2) no ischemia (Control) in thermoneutral conditions (27°C, 50%) with mean skin temperature clamped at 34°C. Thirty seconds after the handgrip exercise, participants cycled for 13.5 min at 40% V̇o2 max. For Occlusion, forearm ischemia was maintained for 9 min followed by no ischemia thereafter. Local sweat rate (SR, ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) on the contralateral nonischemic arm as well as esophageal and skin temperatures were measured continuously. The period of ischemia in the early stages of exercise increased SR (+0.03 mg·cm−2·min−1, P < 0.05) but not CVC ( P > 0.05) above Control levels. No differences were measured in the esophageal temperature at which onset of sweating (Control 37.19 ± 0.09 vs. Occlusion 37.07 ± 0.09°C) or CVC (Control 37.21 ± 0.08 vs. Occlusion 37.08 ± 0.10°C) as well as slopes for these responses (all P > 0.05). However, a greater elevation in SR occurred thereafter such that SR was significantly elevated at the end of the ischemic period relative to Control (0.37 ± 0.05 vs. 0.23 ± 0.05 mg·cm−2·min−1, respectively, P < 0.05) despite no differences in esophageal temperature. We conclude that the activation of forearm muscle metaboreceptor can modulate sweating, but not CVC, during cycling exercise without affecting the core temperature-SR relationship.

We characterized the cardiovascular responses to forearm muscle metaboreflex activation during hypercapnia. Ten healthy males participated under three experimental conditions: 1) hypercapnia (HCA, PetCO2: +10 mmHg, by inhalation of a CO2-enriched gas mixture); 2) muscle metaboreflex activation (MMA, by 5 min of local circulatory occlusion after 1 min of 50% maximum voluntary contraction isometric handgrip under normocapnia); and 3) HCA+MMA. We measured mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO); calculated stroke volume (SV), and total peripheral resistance (TPR); and evaluated myocardial oxygen consumption (MV̇o2) and cardiac work (CW) noninvasively. MAP increased in the three experimental conditions but HCA+MMA led to the highest MAP, CO, and HR. Moreover, HCA+MMA increased SV and was associated with the highest MV̇o2and CW. HCA and MMA exhibited inhibitory interactions with MAP, HR, TPR, MV̇o2, and CW, increases of which were smaller during HCA+MMA than the sum of the increases during HCA and MMA alone (MAP: +28 ± 2 vs. +34 ± 2 mmHg, P < 0.001; HR: +15 ± 2 vs. +22 ± 3 bpm, P < 0.01; TPR: +1.1 ± 1.4 vs. +3.0 ± 1.5 mmHg·l·min−1, P < 0.05; MV̇o2: +50.25 ± 4.74 vs. +59.48 ± 5.37 mmHg·min−1·10−2, P < 0.01; CW: +59.10 ± 7.52 vs. +63.67 ± 7.71 ml mmHg·min−1·10−4, P < 0.05). Oppositely, HCA and MMA interactions were linearly additive for CO (+2.3 ± 0.4 l/min) and SV (+13 ± 4 ml). We showed that muscle metaboreflex and hypercapnia interact in healthy humans, reducing vasoconstriction but enhancing SV.

The present study investigated the role of muscle metaboreceptor activation on human thermoregulation by measuring core temperature thresholds and slopes for sweating and cutaneous vascular responses during passive heating associated with central and peripheral mechanisms. Six male and eight female subjects inserted their lower legs into hot water (43°C) while wearing a water perfusion suit on the upper body (34°C). One minute after immersion, an isometric handgrip exercise—40% of maximum voluntary contraction—was conducted for 1.5 min in both control and experimental conditions, while postexercise occlusion was performed in the experimental condition only for 9 min. The postexercise forearm occlusion during passive heating consistently stimulated muscle metaboreceptors, as implicated by significantly elevated mean arterial blood pressure throughout the experimental period ( P

The cardiopulmonary baroreflex responds to an increase in central venous pressure (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in dogs. However, the direction of ventricular contractility change is not well understood. The aim was to elucidate the cardiopulmonary baroreflex control of ventricular contractility during normal physiological conditions via a mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal ventricular elastance ( Emax), which is perhaps the best available index of ventricular contractility, CVP, arterial blood pressure (ABP), and HR were measured from awake dogs at rest before and after β-adrenergic receptor blockade. An autoregressive exogenous input model was employed to jointly identify the three causal transfer functions relating beat-to-beat fluctuations in CVP to Emax (CVP → Emax), which characterizes the cardiopulmonary baroreflex control of ventricular contractility, ABP to Emax, which characterizes the arterial baroreflex control of ventricular contractility, and HR to Emax, which characterizes the force-frequency relation. The CVP → Emax transfer function showed a static gain of 0.037 ± 0.010 ml−1 (different from zero; P < 0.05) and an overall time constant of 3.2 ± 1.2 s. Hence, Emax would increase and reach steady state in ∼16 s in response to a step increase in CVP, without any change to ABP or HR, due to the cardiopulmonary baroreflex. Following β-adrenergic receptor blockade, the CVP → Emax transfer function showed a static gain of 0.0007 ± 0.0113 ml−1 (different from control; P < 0.10). Hence, Emax would change little in steady state in response to a step increase in CVP. Stimulation of the cardiopulmonary baroreflex increases ventricular contractility through β-adrenergic receptor system mediation.

Activation of muscle metaboreceptors and mechanoreceptors has been shown to independently influence the sweating response, while their integrative control effects remain unclear. We examined the sweating response when the two muscle receptors are concurrently activated in different limbs, as well as the blood pressure response. In total, 27 young males performed passive calf muscle stretches (muscle mechanoreceptor activation) for 30 s in a semisupine position with and without postisometric handgrip exercise muscle ischemia (PEMI, muscle metaboreceptor activation) at exercise intensities of 35 and 50% of maximum voluntary contraction (MVC) under hot conditions (ambient temperature, 35°C, relative humidity, 50%). Passive calf muscle stretching alone increased the mean sweating rate significantly on the forehead, chest, and thigh (SRmean) and mean arterial blood pressure (MAP), but not the heart rate (HR), from prestretching levels by 0.04 ± 0.01 mg·cm2·min−1, 4.0 ± 1.3 mmHg ( P < 0.05), and −1.0 ± 0.5 beats/min ( P > 0.05), respectively. The SRmean and MAP during PEMI were significantly higher than those at rest. The passive calf muscle stretch during PEMI increased MAP significantly by 3.4 ± 1.0 and 2.0 ± 0.7 mmHg for 35 and 50% of MVC, respectively ( P < 0.05), but not that of SRmean or HR at either exercise intensity. These results suggest that sweating and blood pressure responses to concurrent activation of the two muscle receptors in different limbs differ and that the influence of calf muscle mechanoreceptor activation alone on the sweating response disappears during forearm muscle metaboreceptor activation.

We tested the hypotheses that, in humans, changes in cardiac output (CO) and total peripheral vascular resistance (TPR) occurring in response to isometric handgrip exercise vary considerably among individuals and that those individual differences are related to differences in muscle metaboreflex and arterial baroreflex function. Thirty-nine healthy subjects performed a 1-min isometric handgrip exercise at 50% of maximal voluntary contraction. This was followed by a 4-min postexercise muscle ischemia (PEMI) period to selectively maintain activation of the muscle metaboreflex. All subjects showed increases in arterial pressure during exercise. Interindividual coefficients of variation (CVs) for the changes in CO and TPR between rest and exercise periods (CO: 95.1% and TPR: 87.8%) were more than twofold greater than CVs for changes in mean arterial pressure (39.7%). There was a negative correlation between CO and TPR responses during exercise ( r = −0.751, P < 0.01), but these CO and TPR responses correlated positively with the corresponding responses during PEMI ( r = 0.568 and 0.512, respectively, P < 0.01). The CO response during exercise did not correlate with PEMI-induced changes in an index of cardiac parasympathetic tone and cardiac baroreflex sensitivity. These findings demonstrate that the changes in CO and TPR that occur in response to isometric handgrip exercise vary considerably among individuals and that the two responses have an inverse relationship. They also suggest that individual differences in components of the pressor response are attributable in part to variations in muscle metaboreflex-mediated cardioaccelerator and vasoconstrictor responses.

Muscle metaboreflex activation (MMA) during dynamic exercise increases cardiac work and myocardial O2 demand via increases in heart rate, ventricular contractility, and afterload. This increase in cardiac work should lead to metabolic coronary vasodilation; however, no change in coronary vascular conductance occurs. This indicates that the MMA-induced increase in sympathetic activity to the heart, which raises heart rate, ventricular contractility, and cardiac output, also elicits coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired ability to improve left ventricular contractility. In this setting actual coronary vasoconstriction is observed. We tested whether this coronary vasoconstriction could explain, in part, the reduced ability to increase cardiac performance during MMA. In conscious, chronically instrumented dogs before and after pacing-induced heart failure, MMA responses during mild exercise were observed before and after α1-adrenergic blockade (prazosin 20–50 μg/kg). During MMA, the increases in coronary vascular conductance, coronary blood flow, maximal rate of left ventricular pressure change, and cardiac output were significantly greater after α1-adrenergic blockade. We conclude that in subjects with heart failure, coronary vasoconstriction during MMA limits the ability to increase left ventricular contractility.

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Our aim was to determine the muscle metaboreflex threshold and gain in humans by creating an open-loop relationship between active muscle blood flow and hemodynamic responses during a rhythmic handgrip exercise. Eleven healthy subjects performed the exercise at 5 or 15% of maximal voluntary contraction (MVC) in random order. During the exercise, forearm blood flow (FBF), which was continuously measured using Doppler ultrasound, was reduced in five steps by manipulating the inner pressure of an occlusion cuff on the upper arm. The FBF at each level was maintained for 3 min. The initial reductions in FBF elicited no hemodynamic changes, but once FBF fell below a threshold, mean arterial blood pressure (MAP) and heart rate (HR) increased and total vascular conductance (TVC) decreased in a linear manner. The threshold FBF during the 15% MVC trial was significantly higher than during the 5% MVC trial. The gain was then estimated as the slope of the relationship between the hemodynamic responses and FBFs below the threshold. The gains for the MAP and TVC responses did not differ between workloads, but the gain for the HR response was greater in the 15% MVC trial. Our findings thus indicate that increasing the workload shifts the threshold for the muscle metaboreflex to higher blood flows without changing the gain of the reflex for the MAP and TVC responses, whereas it enhances the gain for the HR response.

We examined the degree to which ventilatory sensitivity to rising body temperature (the slope of the regression line relating ventilation and body temperature) is altered by restoration of arterial Pco2 to the eucapnic level during prolonged exercise in the heat. Thirteen subjects exercised for ∼60 min on a cycle ergometer at 50% of peak O2 uptake with and without inhalation of CO2-enriched air. Subjects began breathing CO2-enriched air at the point that end-tidal Pco2 started to decline. Esophageal temperature (Tes), minute ventilation (V̇e), tidal volume (VT), respiratory frequency ( fR), respiratory gases, middle cerebral artery blood velocity, and arterial blood pressure were recorded continuously. When V̇e, VT, fR, and ventilatory equivalents for O2 uptake (V̇e/V̇o2) and CO2 output (V̇e/V̇co2) were plotted against changes in Tes from the start of the CO2-enriched air inhalation (ΔTes), the slopes of the regression lines relating V̇e, VT, V̇e/V̇o2, and V̇e/V̇co2 to ΔTes (ventilatory sensitivity to rising body temperature) were significantly greater when subjects breathed CO2-enriched air than when they breathed room air (V̇e: 19.8 ± 10.3 vs. 8.9 ± 6.7 l·min−1·°C−1, VT: 18 ± 120 vs. −81 ± 92 ml/°C; V̇e/V̇o2: 7.4 ± 5.5 vs. 2.6 ± 2.3 units/°C, and V̇e/V̇co2: 7.6 ± 6.6 vs. 3.4 ± 2.8 units/°C). The increase in V̇e was accompanied by increases in VT and fR. These results suggest that restoration of arterial Pco2 to nearly eucapnic levels increases ventilatory sensitivity to rising body temperature by around threefold.

Ischemia of active skeletal muscle elicits a pressor response termed the muscle metaboreflex. We tested the hypothesis that in normal dogs during dynamic exercise, graded muscle metaboreflex activation (MMA) would progressively attenuate spontaneous heart rate baroreflex sensitivity (SBRS). The animals were chronically instrumented to measure heart rate (HR), cardiac output (CO), mean and systolic arterial pressure (MAP and SAP), and left ventricular systolic pressures (LVSP) at rest and during mild or moderate treadmill exercise before and during progressive MMA [via graded reductions of hindlimb blood flow (HLBF)]. SBRS [slopes of the linear relationships (LRs) between HR and LVSP or SAP during spontaneous sequences of ≥3 consecutive beats when HR changed inversely vs. pressure] decreased during mild exercise from the resting values (−5.56 ± 0.86 vs. −2.67 ± 0.50 beats·min−1·mmHg−1, P −1·mmHg−1, P

We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaboreflex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (−3.08 ± 0.5 vs. −5.14 ± 0.6 beats·min−1·mmHg−1; P < 0.05) and CO-LVSP (−134.74 ± 24.5 vs. −208.6 ± 22.2 ml·min−1·mmHg−1; P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 ± 2.8% vs. 52.3 ± 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation.

Dynamic cardiac baroreflex responses are frequently investigated by analyzing the spontaneous reciprocal changes in arterial pressure and heart rate (HR). However, whether the spontaneous baroreflex-induced changes in HR translate into changes in cardiac output (CO) is unknown. In addition, this linkage between changes in HR and changes in CO may be different in subjects with heart failure (HF). We examined these questions using conscious dogs before and after pacing-induced HF. Spontaneous baroreflex sensitivity in the control of HR and CO was evaluated as the slopes of the linear relationships between HR or CO and left ventricular systolic pressure (LVSP) during spontaneous sequences of greater or equal to three consecutive beats when HR or CO changed inversely versus pressure. Furthermore, the translation of baroreflex HR responses into CO responses (HR-CO translation) was examined by computing the overlap between HR and CO sequences. In normal resting conditions, 44.0 ± 4.4% of HR sequences overlapped with CO sequences, suggesting that only around half of the baroreflex HR responses cause CO responses. In HF, HR-LVSP, CO-LVSP, and the HR-CO translation significantly decreased compared with the normal condition (−2.29 ± 0.5 vs. −5.78 ± 0.7 beats·min−1·mmHg−1; −70.95 ± 11.8 vs. −229.89 ± 29.6 ml·min−1·mmHg−1; and 19.66 ± 4.9 vs. 44.0 ± 4.4%, respectively). We conclude that spontaneous baroreflex HR responses do not always cause changes in CO. In addition, HF significantly decreases HR-LVSP, CO-LVSP, and HR-CO translation.

In heart failure (HF), there is a reduced baroreflex sensitivity at rest, and during dynamic exercise there is enhanced muscle metaboreflex activation (MRA). However, how the arterial baroreflex modulates HR during exercise is unknown. We tested the hypothesis that spontaneous baroreflex sensitivity (SBRS) is attenuated during exercise in HF and that MRA further depresses SBRS. In seven conscious dogs we measured heart rate (HR), cardiac output, and left ventricular systolic pressure at rest and during mild and moderate dynamic exercise, before and during MRA (via imposed reductions of hindlimb blood flow), and before and after induction of HF (by rapid ventricular pacing). SBRS was assessed by the sequences method. In control, SBRS was reduced from rest with a progressive resetting of the baroreflex stimulus-response relationship in proportion to exercise intensity and magnitude of MRA. In HF, SBRS was significantly depressed in all settings; however, the changes with exercise and MRA occurred with a pattern similar to the control state. As in control, the baroreflex stimulus-response relationship showed an intensity- and muscle metaboreflex (MMR)-dependent rightward and upward shift. The results of this study indicate that HF induces an impairment in baroreflex control of HR at rest and during exercise, although the effects of exercise and MRA on SBRS occur with a similar pattern as in control, indicating the persistence of some vagal activity.

Continuous measurement of leg blood flow (LBF) using Doppler ultrasound with simultaneous noninvasive mean arterial blood pressure (MAP) measurement permits beat-to-beat estimates of leg vascular resistance (LVR) in humans. We tested the hypothesis that the beat-to-beat fluctuations in LVR and the dynamic relationship between MAP and LVR are modulated by the activation of muscle metaboreflex. Twelve healthy subjects performed a 1-min isometric handgrip exercise at 50% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). We then employed transfer function analysis to examine the dynamic relationships between MAP and LBF and between MAP and LVR, both at rest (control) and during PEMI. We found the following. 1) The spectral power for LBF and LVR in low-frequency ( approximately 0.03-0.15 Hz) range significantly increased from control during PEMI without a significant change in the high-frequency ( approximately 0.15-0.35 Hz) power. 2) During PEMI, the transfer function gains for MAP-LBF and MAP-LVR relationships in the low-frequency ( approximately 0.05-0.15 Hz) range were significantly increased during PEMI (vs. control) but were unchanged in the high-frequency ( approximately 0.2-0.3 Hz) range. 3) The phases for MAP-LBF and MAP-LVR relationships were not different during control and PEMI. The phase for MAP-LVR relationship revealed that changes in MAP were followed by directionally similar changes in LVR, which is consistent with the characteristics of intrinsic vascular regulatory mechanisms such as the myogenic response of the resistance arteries. We suggest that, in humans, modulation of the dynamic MAP-LVR relationship during activation of the muscle metaboreflex reflects complex interactions between intrinsic vascular regulatory mechanisms and sympathetic vascular regulation.

We tested the hypothesis that peripheral vascular responses (in the lower and upper limbs) to application of lower body positive pressure (LBPP) are dependent on the posture of the subjects. We measured heart rate, stroke volume, mean arterial pressure, leg and forearm blood flow (using the Doppler ultrasound technique), and leg (LVC) and forearm (FVC) vascular conductance in 11 subjects (9 men, 2 women) without and with LBPP (25 and 50 mmHg) in supine and upright postures. Mean arterial pressure increased in proportion to increases in LBPP and was greater in supine than in upright subjects. Heart rate was unchanged when LBPP was applied to supine subjects but was reduced in upright ones. Leg blood flow and LVC were both reduced by LBPP in supine subjects [LVC: 4.8 (SD 4.0), 3.6 (SD 3.5), and 1.4 (SD 1.8) ml·min−1·mmHg−1 before LBPP and during 25 and 50 mmHg LBPP, respectively; P < 0.05] but were increased in upright ones [LVC: 2.0 (SD 1.2), 3.4 (SD 3.4), and 3.0 (SD 2.0) ml·min−1·mmHg−1, respectively; P < 0.05]. Forearm blood flow and FVC both declined when LBPP was applied to supine subjects [FVC: 1.3 (SD 0.6), 1.0 (SD 0.4), and 0.9 (SD 0.6) ml· min−1·mmHg−1, respectively; P < 0.05] but remained unchanged in upright ones [FVC: 0.7 (SD 0.4), 0.7 (SD 0.4), and 0.6 (SD 0.5) ml·min−1·mmHg−1, respectively]. Together, these findings indicate that the leg vascular response to application of LBPP is posture dependent and that the response differs in the lower and upper limbs when subjects assume an upright posture.

Ischemia of active skeletal muscle evokes a powerful blood pressure-raising reflex termed the muscle metaboreflex (MMR). MMR activation increases cardiac sympathetic nerve activity, which increases heart rate, ventricular contractility, and cardiac output (CO). However, despite the marked increase in ventricular work, no coronary vasodilation occurs. Using conscious, chronically instrumented dogs, we observed MMR-induced changes in arterial pressure, CO, left circumflex coronary blood flow (CBF), and coronary vascular conductance (CVC) before and after α1-receptor blockade (prazosin, 100 μg/kg iv). MMR was activated during mild treadmill exercise by partially reducing hindlimb blood flow. In control experiments, MMR activation caused a substantial pressor response-mediated via increases in CO. Although CBF increased (+28.1 ± 3.7 ml/min; P < 0.05), CVC did not change (0.45 ± 0.05 vs. 0.47 ± 0.06 ml·min−1·mmHg−1, exercise vs. exercise with MMR activation, respectively; P > 0.05). Thus all of the increase in CBF was due to the increase in arterial pressure. In contrast, after prazosin, MMR activation caused a greater increase in CBF (+55.9 ± 17.1 ml/min; P < 0.05 vs. control) and CVC rose significantly (0.59 ± 0.08 vs. 0.81 ± 0.17 ml·min−1·mmHg−1, exercise vs. exercise with MMR activation, respectively; P < 0.05). A greater increase in CO also occurred (+2.01 ± 0.1 vs. +3.27 ± 1.1 l/min, control vs. prazosin, respectively; P < 0.05). We conclude that the MMR-induced increases in sympathetic activity to the heart functionally restrain coronary vasodilation, which may limit increases in ventricular function.

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: −15 and −35 mmHg). At −15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at −35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at −15 mmHg LBNP (vs. CON) and further shifted upward at −35 mmHg LBNP. At −15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at −35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.

We aimed to investigate the interaction [with respect to the regulation of muscle sympathetic nerve activity (MSNA) and blood pressure] between the arterial baroreflex and muscle metaboreflex in humans. In 10 healthy subjects who performed a 1-min sustained handgrip exercise at 50% maximal voluntary contraction followed by forearm occlusion, arterial baroreflex control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between beat-by-beat spontaneous variations in diastolic arterial blood pressure (DAP) and MSNA both during supine rest (control) and during postexercise muscle ischemia (PEMI). During PEMI (vs. control), 1) the linear relationship between burst incidence and DAP was shifted rightward with no alteration in sensitivity, 2) the linear relationship between burst strength and DAP was shifted rightward and upward with no change in sensitivity, and 3) the linear relationship between total activity and DAP was shifted to a higher blood pressure and its sensitivity was increased. The modification of the control of total activity that occurs in PEMI could be a consequence of alterations in the baroreflex control of both MSNA burst incidence and burst strength. These results suggest that the arterial baroreflex and muscle metaboreflex interact to control both the occurrence and strength of MSNA bursts.