Responses in muscle sympathetic nerve activity to sustained hand-grips of different tensions in humans

To clarify whether sympathetic nerve activity increases in relation to the tension of a sustained muscle contraction, muscle sympathetic nerve activity (MSA) was recorded directly from the peroneal nerve fascicle at the popliteal fossa by means of tungsten microelectrodes in five healthy male subjects. A sustained muscle contraction was performed by handgrip for two minutes in a supine position at tensions of 10, 30 and 45% of maximal grip strength (MGS). MSA, electrocardiogram (ECG) using bipolar electrodes from the chest and surface electromyogram (EMG) from the extensor pollicis longus were recorded simultaneously before and during the sustained handgrip. Arterial blood pressure was measured at the resting upper arm by auscultation. During handgrip with tensions of 10, 30 and 45% MGS, average MSA burst rate (bursts X min-1) increased to 122, 152 and 230% of the resting value, respectively. During the same experimental procedures with tensions of 10, 30 and 45% MGS, average heart rate increased to 105, 110 and 111% of the resting value. These results confirm that sympathetic outflow to a resting muscle is increased with elevation of tension in an active muscle. This process would promote perfusion pressure in the active muscle.     

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.     

Hemodynamics and muscle sympathetic nerve activity after 8 h of sustained hypoxia in healthy humans

Hemodynamics, muscle sympathetic nerve activity (MSNA), and forearm blood flow were evaluated in 12 normal subjects before, during (1 and 7 h), and after ventilatory acclimatization to hypoxia achieved with 8 h of continuous poikilocapnic hypoxia. All results are means +/- SD. Subjects experienced mean oxygen saturation of 84.3 +/- 2.3% during exposure. The exposure resulted in hypoxic acclimatization as suggested by end-tidal CO(2) [44.7 +/- 2.7 (pre) vs. 39.5 +/- 2.2 mmHg (post), P < 0.001] and by ventilatory response to hypoxia [1.2 +/- 0.8 (pre) vs. 2.3 +/- 1.3 l x min(-1).1% fall in saturation(-1) (post), P < 0.05]. Subjects exhibited a significant increase in heart rate across the exposure that remained elevated even upon return to room air breathing compared with preexposure (67.3 +/- 15.9 vs. 59.8 +/- 12.1 beats/min, P < 0.008). Although arterial pressure exhibited a trend toward an increase across the exposure, this did not reach significance. MSNA initially increased from room air to poikilocapnic hypoxia (26.2 +/- 10.3 to 32.0 +/- 10.3 bursts/100 beats, not significant at 1 h of exposure); however, MSNA then decreased below the normoxic baseline despite continued poikilocapnic hypoxia (20.9 +/- 8.0 bursts/100 beats, 7 h Hx vs. 1 h Hx; P < 0.008 at 7 h). MSNA decreased further after subjects returned to room air (16.6 +/- 6.0 bursts/100 beats; P < 0.008 compared with baseline). Forearm conductance increased after exposure from 2.9 +/- 1.5 to 4.3 +/- 1.6 conductance units (P < 0.01). These findings indicate alterations of cardiovascular and respiratory control following 8 h of sustained hypoxia producing not only acclimatization but sympathoinhibition.     

Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans.

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end, we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O(2) saturation nadir 81.4 +/- 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA from 113 +/- 11 to 159 +/- 21 units/min (P = 0.001) and mean blood pressure from 92.1 +/- 2.9 to 95.5 +/- 2.9 mmHg (P = 0.01; n = 19). Furthermore, compared with before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia [fraction of inspired O(2) (Fi(O(2))) 0.1, for 5 min] were enhanced (pre- vs. post-intermittent hypoxia: +16 +/- 4 vs. +49 +/- 10%; P = 0.02; n = 11), whereas the responses to hyperoxia (Fi(O(2)) 0.5, for 5 min) were not changed significantly (P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.     

Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans.

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20-33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O(2)). Compared with normoxia, hypoxia reduced arterial O(2) saturation levels from 96.8 +/- 0.3 to 80.7 +/- 1.4% (P < 0.001), increased heart rate from 59.8 +/- 2.4 to 79.4 +/- 2.9 beats/min (P < 0.001), increased mean arterial pressure from 96.7 +/- 2.5 to 105.0 +/- 3.3 mmHg (P = 0.002), and increased sympathetic activity 126 +/- 58% (P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: -1.02 +/- 0.09 vs. -1.02 +/- 0.11 beats. min(-1). mmHg(-1); nerve activity: -5.6 +/- 0.9 vs. -6.2 +/- 0.9 integrated activity. beat(-1). mmHg(-1); both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.     

Spectral analysis of muscle sympathetic nerve activity in heat-stressed humans

Whole body heating increases muscle sympathetic nerve activity (MSNA); however, the effect of heat stress on spectral characteristics of MSNA is unknown. Such information may provide insight into mechanisms of heat stress-induced MSNA activation. The purpose of the present study was to test the hypothesis that heat stress-induced changes in systolic blood pressure variability parallel changes in MSNA variability. In 13 healthy subjects, MSNA, electrocardiogram, arterial blood pressure (via Finapres), and respiratory activity were recorded under both normothermic and heat stress conditions. Spectral characteristics of integrated MSNA, R-R interval, systolic blood pressure, and respiratory excursions were assessed in the low (LF; 0.03-0.15 Hz) and high (HF; 0.15-0.45 Hz) frequency components. Whole body heating significantly increased skin and core body temperature, MSNA burst rate, and heart rate, but not mean arterial blood pressure. Systolic blood pressure and R-R interval variability were significantly reduced in both the LF and HF ranges. Compared with normothermic conditions, heat stress significantly increased the HF component of MSNA, while the LF component of MSNA was not altered. Thus the LF-to-HF ratio of MSNA oscillatory components was significantly reduced. These data indicate that the spectral characteristics of MSNA are altered by whole body heating; however, heat stress-induced changes in MSNA do not parallel changes in systolic blood pressure variability. Moreover, the reduction in LF component of systolic blood pressure during heat stress is unlikely related to spectral changes in MSNA.     

Exposure to hypoxia produces long-lasting sympathetic activation in humans.

The relative contributions of hypoxia and hypercapnia in causing persistent sympathoexcitation after exposure to the combined stimuli were assessed in nine healthy human subjects during wakefulness. Subjects were exposed to 20 min of isocapnic hypoxia (arterial O(2) saturation, 77-87%) and 20 min of normoxic hypercapnia (end-tidal P(CO)(2), +5.3-8.6 Torr above eupnea) in random order on 2 separate days. The intensities of the chemical stimuli were manipulated in such a way that the two exposures increased sympathetic burst frequency by the same amount (hypoxia: 167 +/- 29% of baseline; hypercapnia: 171 +/- 23% of baseline). Minute ventilation increased to the same extent during the first 5 min of the exposures (hypoxia: +4.4 +/- 1.5 l/min; hypercapnia: +5.8 +/- 1.7 l/min) but declined with continued exposure to hypoxia and increased progressively during exposure to hypercapnia. Sympathetic activity returned to baseline soon after cessation of the hypercapnic stimulus. In contrast, sympathetic activity remained above baseline after withdrawal of the hypoxic stimulus, even though blood gases had normalized and ventilation returned to baseline levels. Consequently, during the recovery period, sympathetic burst frequency was higher in the hypoxia vs. the hypercapnia trial (166 +/- 21 vs. 104 +/- 15% of baseline in the last 5 min of a 20-min recovery period). We conclude that both hypoxia and hypercapnia cause substantial increases in sympathetic outflow to skeletal muscle. Hypercapnia-evoked sympathetic activation is short-lived, whereas hypoxia-induced sympathetic activation outlasts the chemical stimulus.     

Differential regulation of sympathetic burst frequency and amplitude following acute hypoxia in humans

Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed after exposure to hypoxia (HX), is mediated by chemoreceptor sensitization and or baroreflex resetting. Evidence in humans and animals suggests that these reflexes may independently regulate the frequency (gating) and amplitude (neuronal recruitment) of SNA bursts. In humans (n = 7), we examined the regulation of SNA following acute isocapnic HX (5 min; end-tidal Po(2) = 45 Torr) and euoxic hypercapnia (HC; 5 min; end-tidal Pco(2) = +10 from baseline). HX increased SNA burst frequency (21 ± 7 to 28 ± 8 bursts/min, P < 0.05) and amplitude (99 ± 10 to 125 ± 19 au, P < 0.05) as did HC (14 ± 6 to 22 ± 10 bursts/min, P < 0.05 and 100 ± 12 to 133 ± 29 au, P < 0.05, respectively). Burst frequency (26 ± 7 bursts/min, P < 0.05), but not amplitude (97 ± 12 au), remained elevated 10 min post-HX. The change in burst amplitude (but not frequency) was significantly related to the measured change in ventilation (r(2) = 0.527, P < 0.001). Both frequency and amplitude decreased during recovery following HC. These data indicate the differential regulation of pattern and magnitude of sympathetic outflow in humans with sympathetic persistence following HX being specific to burst frequency and not amplitude.     

Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans

We compared the effects of isocapnic hypoxia (IHO) and hyperoxic hypercapnia (HC) on sympathetic nerve activity (SNA) recorded from a peroneal nerve in 13 normal subjects. HC caused greater increases in blood pressure (BP), minute ventilation (VE), and SNA [53 +/- 14% (SE) during HC vs. 21 +/- 7% during IHO; P less than 0.05]. Even at equivalent levels of VE, HC still elicited greater SNA than IHO. However, apnea during HC caused a lesser (P less than 0.05) increase in SNA (91 +/- 26% compared with apnea on room air) than apnea during IHO (173 +/- 50%). Hypercapnic hypoxia resulted in a greater absolute increase in VE (23.6 +/- 2.8 l/min) than the additive increases due to HC alone plus IHO alone (18.0 +/- 1.8 l/min, P less than 0.05). SNA also increased synergistically by 108 +/- 23% with the combined stimulus compared with the additive effect of HC alone plus IHO alone (68 +/- 19%; P less than 0.05). We conclude that 1) HC causes greater increases in VE and SNA than does hypoxia; 2) for the same increase in VE, hypercapnia still causes a greater increase in SNA than hypoxia; however, during apnea, hypoxia causes a much greater increase in SNA than hypercapnia; 3) the inhibitory influence of ventilation on SNA is greater during hypoxia (i.e., predominantly peripheral chemoreceptor stimulation) than hypercapnia (i.e., predominantly central chemoreceptor stimulation); and 4) combined hypoxia and hypercapnia have a synergistic effect on SNA as well as on VE.     

Hypoxemia raises muscle sympathetic activity but not norepinephrine in resting humans

The experimental objective was to determine whether moderate to severe hypoxemia increases skeletal muscle sympathetic nervous activity (MSNA) in resting humans without increasing venous plasma concentrations of norepinephrine (NE) and epinephrine (E). In nine healthy subjects (20-34 yr), we measured MSNA (peroneal nerve), venous plasma levels of NE and E, arterial blood pressure, heart rate, and end-tidal O2 and CO2 before (control) and during breathing of 1) 12% O2 for 20 min, 2) 10% O2 for 20 min, and 3) 8% O2 for 10 min--in random order. MSNA increased above control in five, six, and all nine subjects during 12, 10, and 8% O2, respectively (P less than 0.01), but only after delays of 12 (12% O2) and 4 min (8 and 10% O2). MSNA (total activity) rose 83 +/- 20, 260 +/- 146, and 298 +/- 109% (SE) above control by the final minute of breathing 12, 10, and 8% O2, respectively. NE did not rise above control at any level of hypoxemia; E rose slightly (P less than 0.05) at one time only with both 10 and 8% O2. Individual changes in MSNA during hypoxemia were unrelated to elevations in heart rate or decrements in blood pressure and end-tidal CO2--neither of which always fell. We conclude that in contrast to some other sympathoexcitatory stimuli such as exercise or cold stress, moderate to severe hypoxemia increases leg MSNA without raising plasma NE in resting humans.     

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

Background

Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.

Methods

Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂ = 80%) and hyperoxic (FiO₂ = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.

Results

Hypoxia enhanced hyperpnoea-induced P_di,tw and P_ga,tw reductions both immediately after hyperpnoea (P_di,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (P_di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in P_di,tw or P_ga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.

Conclusions

These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂ transport as during exercise in altitude or in hypoxemic patients.     

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.     

Dissociation of muscle sympathetic nerve activity and leg vascular resistance in humans

We examined the hypothesis that the increase in inactive leg vascular resistance during forearm metaboreflex activation is dissociated from muscle sympathetic nerve activity (MSNA). MSNA (microneurography), femoral artery mean blood velocity (FAMBV, Doppler), mean arterial pressure (MAP), and heart rate (HR) were assessed during fatiguing static handgrip exercise (SHG, 2 min) followed by posthandgrip ischemia (PHI, 2 min). Whereas both MAP and MSNA increase during SHG, the transition from SHG to PHI is characterized by a transient reduction in MAP but sustained elevation in MSNA, facilitating separation of these factors in vivo. Femoral artery vascular resistance (FAVR) was calculated (MAP/MBV). MSNA increased by 59 +/- 20% above baseline during SHG (P < 0.05) and was 58 +/- 18 and 78 +/- 18% above baseline at 10 and 20 s of PHI, respectively (P < 0.05 vs. baseline). Compared with baseline, FAVR increased 51 +/- 22% during SHG (P < 0.0001) but returned to baseline levels during the first 30 s of PHI, reflecting the changes in MAP (P < 0.005) and not MSNA. It was concluded that control of leg muscle vascular resistance is sensitive to changes in arterial pressure and can be dissociated from sympathetic factors.     

Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans

Evidence from animalsindicates that skeletal muscle afferents activate the vestibular nucleiand that both vestibular and skeletal muscle afferents have inputs tothe ventrolateral medulla. The purpose of the present study was toinvestigate the interaction between the vestibulosympathetic andskeletal muscle reflexes on muscle sympathetic nerve activity (MSNA)and arterial pressure in humans. MSNA, arterial pressure, and heartrate were measured in 17 healthy subjects in the prone position duringthree experimental trials. The three trials were 2 min of 1)head-down rotation (HDR) to engage the vestibulosympathetic reflex,2) isometric handgrip (IHG) at 30% maximal voluntarycontraction to activate skeletal muscle afferents, and 3)HDR and IHG performed simultaneously. The order of the three trials wasrandomized. HDR and IHG performed alone increased total MSNA by 46 ± 16 and 77 ± 24 units, respectively (P < 0.01). During the HDR plus IHG trial, MSNA increased 142 ± 38 units (P < 0.01). This increase was not significantlydifferent from the sum of the individual trials (130 ± 41 units).This finding was also observed with mean arterial pressure (sum = 21 ± 2 mmHg and HDR + IHG = 22 ± 2 mmHg). Thesefindings suggest that there is an additive interaction for MSNA andarterial pressure when the vestibulosympathetic and skeletal musclereflexes are engaged simultaneously in humans. Therefore, no centralmodulation exists between these two reflexes with regard to MSNA outputin humans.

     

Basis for the cardiac-related rhythm in muscle sympathetic nerve activity of humans

We tested the hypothesis that the cardiac-related rhythm in muscle sympathetic nerve activity (MSNA) of humans reflects entrainment of a central oscillator by pulse-synchronous baroreceptor nerve activity. Partial autospectral analysis was used to mathematically remove the portion of cardiac-related power in MSNA autospectra that was attributable to its linear relationship to the ECG. In 54 of 98 cases, > or =15% of cardiac-related power remained after partialization with the ECG; peak residual cardiac-related power was often at a frequency different than heart rate. When assessed on a cardiac-related burst-by-burst basis, there was a progressive and cyclic change in the ECG-MSNA interval (delay from R wave to peak of cardiac-related burst) on the time scale of respiration in four subjects. In these subjects, as well as in some in which the interval appeared to change randomly, there was an inverse relationship between the ECG-MSNA interval and cardiac-related burst amplitude. However, in 45% of the cases, these parameters were not related. These results support the view that the cardiac-related rhythm in MSNA reflects forcing of a nonlinear oscillator rather than periodic inhibition of unstructured, random activity.     

Postexercise responses of muscle sympathetic nerve activity and blood flow to hyperinsulinemia in humans.

Although insulin and exercise cause dramatic changes in physiological parameters, the impact of exercise on neural and hemodynamic responses to insulin administration has not been described. In a study of the effects of a single bout of exercise on blood pressure (BP), muscle sympathetic nerve activity (MSNA), and forearm blood flow (FBF) responses to insulin infusion during the postexercise period, 11 healthy men underwent, in a random order, two hyperinsulinemic euglycemic clamps performed after 45 min of 1) bicycle exercise (50% peak O(2) uptake, Exercise session) and 2) seated rest (Control session). Data were analyzed during baseline and steady-state periods. Although insulin levels and insulin sensitivity were similar, baseline plasma glucose levels were significantly lower in the Exercise than in the Control session. Mean BP was significantly lower (3%) and FBF was higher (27%) in the Exercise session. Exercise increased insulin-induced MSNA enhancement (84%) without changing FBF and BP responses to hyperinsulinemia. In conclusion, a single bout of exercise that does not alter insulin sensitivity exacerbates insulin-induced increase in MSNA without changing FBF and BP responses to hyperinsulinemia.     

Modulation of arterial baroreflex control of muscle sympathetic nerve activity by muscle metaboreflex in humans

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.     

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.     

Erythropoietin response to acute normobaric hypoxia in humans.

Hypoxia causes an increased production of erythropoietin (EPO), but the time course of the EPO response in humans has not been well characterized. This study examines the relationship between the duration of normobaric hypoxic exposure and plasma EPO levels in healthy human subjects. Six volunteers breathed a gas mixture of 10.5% O2-89.5% N2 continuously for 5, 60, and 120 or intermittently for 240 min. O2 saturations were maintained between 75 and 85% during the exposure. Arterial pH was 7.467 +/- 0.019, PO2 37.05 +/- 2.43 Torr, and PCO2 36.69 +/- 2.05 Torr. O2 half-saturation pressures of hemoglobin were normal for all subjects. Plasma EPO was measured every 30 min for 360 min by radioimmunoassay. No increase in EPO was seen after the 5- and 60-min exposures. However, a 50% increase was seen 240 min after the initiation of the 120-min hypoxic exposure (P less than 0.01). Intermittent exposure resulted in an increase of EPO by 52% 360 min after the onset of exposure (P less than 0.05). Therefore, exposing humans continuously to an inspiratory O2 fraction of 0.105 for 120 min or intermittently for 240 min provides a sufficient stimulus to increase production of EPO.