Time-dependent modulation of arterial baroreflex control of muscle sympathetic nerve activity during isometric exercise in humans

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

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.     

Arterial baroreflex control of muscle sympathetic nerve activity in the transition from rest to steady-state dynamic exercise in humans

We sought to investigate arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) in the transition from rest to steady-state dynamic exercise. This was accomplished by assessing the relationship between spontaneous variations in diastolic blood pressure (DBP) and MSNA at rest and during the time course of reaching steady-state arm cycling at 50% peak oxygen uptake (VO(2peak)). Specifically, DBP-MSNA relations were examined in eight subjects (25 +/- 1 yr) at the start of unloaded arm cycling and then during the initial and a later period of arm cycling once the 50% VO(2peak) work rate was achieved. Heart rate and arterial blood pressure were progressively increased throughout exercise. Although resting MSNA [16 +/- 2 burst/min; 181 +/- 36 arbitrary units (au) total activity] was unchanged during unloaded cycling, MSNA burst frequency and total activity were significantly elevated during the initial (27 +/- 4 burst/min; 367 +/- 76 au; P < 0.05) and later (36 +/- 7 burst/min; 444 +/- 91 au; P < 0.05) periods of exercise. The relationships between DBP and burst incidence, burst strength, and total MSNA were progressively shifted rightward from unloaded to the initial to the later period of 50% VO(2peak) arm cycling without any changes in the slopes of the linear regressions (i.e., ABR sensitivity). Thus a continuous and dynamic resetting of the ABR control of MSNA occurred during the transition from rest to steady-state dynamic exercise. These findings indicate that the ABR control of MSNA was well maintained throughout dynamic exercise in humans, progressively being reset to operate around the exercise-induced elevations in blood pressure and MSNA without any changes in reflex sensitivity.     

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans.

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.     

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling.

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 +/- 0.2 to 29.8 +/- 0.6 degrees C; P < 0.001) and increased mean arterial blood pressure (85 +/- 2 to 93 +/- 3 mmHg; P < 0.001) without changing MSNA (P = 0.47) or heart rate (P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (-3.54 +/- 0.29 units.beat(-1).mmHg(-1)) was not significantly different from normothermic conditions (-2.94 +/- 0.21 units.beat(-1).mmHg(-1); P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the "operating point" of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.     

Spontaneous baroreflex control of heart rate during exercise and muscle metaboreflex activation in heart failure

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.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.     

Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans

Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.     

Modulation of the spontaneous beat-to-beat fluctuations in peripheral vascular resistance during activation of muscle metaboreflex

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.     

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (> 0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)?1)·mmHg?1; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)?1 mmHg?1; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)?1·mmHg?1; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.     

Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/- 0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.     

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.     

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans

Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10 degrees head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased approximately 2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 +/- 0.6 and -3.3 +/- 1.0 versus -5.0 +/- 0.6 units.beat(-1).mmHg(-1) (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans.     

Modulation of cardiac contractility by muscle metaboreflex following efforts of different intensities in humans

Accumulation of metabolic end products within skeletal muscle stimulates sensory nerves, thus evoking a pressor response termed "metaboreflex." The aim of this study was to evaluate changes in hemodynamics occurring during metaboreflex activation obtained by postexercise muscle ischemia (PEMI) after two different exercise intensities. In twelve healthy subjects, the metaboreflex was studied with the PEMI method at the start of recovery from one leg-dynamic knee extension performed at intensities of 30% (PEMI 30%) and 70% (PEMI 70%) of the maximum workload achieved in a preliminary test. Control exercise recovery tests at the same intensities were also conducted. Central hemodynamics were evaluated by means of impedance cardiography. The main findings were that 1) during metaboreflex, exercise conducted against the higher workload caused a more pronounced blood pressure increase than the strain conducted against the lower workload; and 2) during PEMI 70%, this blood pressure response was mainly achieved through enhancement of myocardial contractility that increased stroke volume and, in turn, cardiac output, whereas during PEMI 30%, the blood pressure response was reached predominantly by means of vasoconstriction. Thus a substantial enhancement of myocardial contractility was reached only in the PEMI 70% test. These results suggest that hemodynamic regulation during metaboreflex engagement caused by PEMI in humans is dependent on the intensity of the previous effort. Moreover, the cardiovascular response during metaboreflex is not merely achieved by vasoconstriction alone, but it appears that there is a complex interplay between peripheral vasoconstriction and heart contractility recruitment.     

Static handgrip exercise modifies arterial baroreflex control of vascular sympathetic outflow in humans

To examine effects of static exercise on the arterial baroreflex control of vascular sympathetic nerve activity, 22 healthy male volunteers performed 2 min of static handgrip exercise at 30% of maximal voluntary force, followed by postexercise circulatory arrest (PE-CA). Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of arterial pressure (Portapres). The relationship between MSNA and diastolic arterial pressure was calculated for each condition and was defined as the arterial baroreflex function. There was a close relationship between MSNA and diastolic arterial pressure in each subject at rest and during static exercise and PE-CA. The slope of the relationship significantly increased by >300% during static exercise (P < 0.001), and the x-axis intercept (diastolic arterial pressure level) increased by 13 mmHg during exercise (P < 0.001). These alterations in the baroreflex relationship were completely maintained during PE-CA. It is concluded that static handgrip exercise is associated with a resetting of the operating range and an increase in the reflex gain of the arterial barorelex control of MSNA.     

Muscle metaboreflex modulates the arterial baroreflex dynamic effects on peripheral vascular conductance in humans

We aimed to investigate the interaction between the arterial baroreflex and muscle metaboreflex [as reflected by alterations in the dynamic responses shown by leg blood flow (LBF: by the ultrasound Doppler method), leg vascular conductance (LVC), mean arterial blood pressure (MAP), and heart rate (HR)] in humans. In 12 healthy subjects (10 men and 2 women), who performed sustained 1-min handgrip exercise at 50% maximal voluntary contraction followed immediately by an imposed postexercise muscle ischemia (PEMI), 5-s periods of neck pressure (NP; 50 mmHg) or neck suction (NS; -60 mmHg) were used to evaluate carotid baroreflex function both at rest (Con) and during PEMI. First, the decreases in LVC and LBF and the augmentation of MAP elicited by NP were all greater during PEMI than in Con (DeltaLVC, -1.2 +/- 0.2 vs. -1.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, -97.3 +/- 11.2 vs. -177.0 +/- 21.8 ml/min; DeltaMAP, 6.7 +/- 1.2 vs. 11.5 +/- 1.4 mmHg, Con vs. PEMI; each P < 0.05). Second, in Con, NS significantly increased both LVC and LBF (DeltaLVC, 0.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, 46.6 +/- 9.8 ml/min; significant change from baseline: each P < 0.05), and, whereas during PEMI no significant increases in LVC and LBF occurred during NS itself (DeltaLVC, 0.2 +/- 0.1 ml.min(-1).mmHg(-1); DeltaLBF, 10.8 +/- 9.6 ml/min; each P > 0.05), a decrease was evident in each parameters at 5 s after the cessation of NS. Third, during PEMI, the decrease in MAP elicited by NS was smaller (DeltaMAP, -8.4 +/- 1.0 vs. -5.8 +/- 0.4 mmHg, Con vs. PEMI; P < 0.05), and it recovered to its initial level more quickly after NS (vs. Con). Finally, however, the HR responses to NS and NP were not different between PEMI and Con. These results suggest that during muscle metaboreflex activation in humans, the arterial baroreflex dynamic effect on peripheral vascular conductance is modulated, as exemplified by 1) an augmentation of the NP-induced LVC decrease, and 2) a loss of the NS-induced LVC increase.     

Arterial baroreflex alters strength and mechanisms of muscle metaboreflex during dynamic exercise

Previous studies showed that the arterial baroreflex opposes the pressor response mediated by muscle metaboreflex activation during mild dynamic exercise. However, no studies have investigated the mechanisms contributing to metaboreflex-mediated pressor responses during dynamic exercise after arterial baroreceptor denervation. Therefore, we investigated the contribution of cardiac output (CO) and peripheral vasoconstriction in mediating the pressor response to graded reductions in hindlimb perfusion in conscious, chronically instrumented dogs before and after sinoaortic denervation (SAD) during mild and moderate exercise. In control experiments, the metaboreflex pressor responses were mediated via increases in CO. After SAD, the metaboreflex pressor responses were significantly greater and significantly smaller increases in CO occurred. During control experiments, nonischemic vascular conductance (NIVC) did not change with muscle metaboreflex activation, whereas after SAD NIVC significantly decreased with metaboreflex activation; thus SAD shifted the mechanisms of the muscle metaboreflex from mainly increases in CO to combined cardiac and peripheral vasoconstrictor responses. We conclude that the major mechanism by which the arterial baroreflex buffers the muscle metaboreflex is inhibition of metaboreflex-mediated peripheral vasoconstriction.     

Baroreflex control of muscle sympathetic nerve activity as a mechanism for persistent sympathoexcitation following acute hypoxia in humans

This study tested the hypothesis that acute isocapnic hypoxia results in persistent resetting of the baroreflex to higher levels of muscle sympathetic nerve activity (MSNA), which outlasts the hypoxic stimulus. Cardiorespiratory measures were recorded in humans (26 ± 1 yr; n = 14; 3 women) during baseline, exposure to 20 min of isocapnic hypoxia, and for 5 min following termination of hypoxia. The spontaneous baroreflex threshold technique was used to determine the change in baroreflex function during and following 20 min of isocapnic hypoxia (oxyhemoglobin saturation = 80%). From the spontaneous baroreflex analysis, the linear regression between diastolic blood pressure (DBP) and sympathetic burst occurrence, the T50 (DBP with a 50% likelihood of a burst occurring), and DBP error signal (DBP minus the T50) provide indexes of baroreflex function. MSNA and DBP increased in hypoxia and remained elevated during posthypoxia relative to baseline (P < 0.05). The DBP error signal became progressively less negative (i.e., smaller difference between DBP and T50) in the hypoxia and posthypoxia periods (baseline: -3.9 ± 0.8 mmHg; hypoxia: -1.4 ± 0.6 mmHg; posthypoxia: 0.2 ± 0.6 mmHg; P < 0.05). Hypoxia caused no change in the slope of the baroreflex stimulus-response curve; however, there was a shift toward higher pressures that favored elevations in MSNA, which persisted posthypoxia. Our results indicate that there is a resetting of the baroreflex in hypoxia that outlasts the stimulus and provide further explanation for the complex control of MSNA following acute hypoxia.     

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.