Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea.

Obstructive sleep apnea (OSA) is associated with transient elevation of muscle sympathetic nerve activity (MSNA) during apneic events, which often produces elevated daytime MSNA in OSA patients. Hypoxia is postulated to be the primary stimulus for elevated daytime MSNA in OSA patients. Therefore, we studied the effects of 20 min of intermittent voluntary hypoxic apneas on MSNA during 180 min of recovery. Also, we compared MSNA during recovery after either 20 min of intermittent voluntary hypoxic apneas, hypercapnic hypoxia, or isocapnic hypoxia. Consistent with our hypothesis, both total MSNA and MSNA burst frequency were elevated after 20 min of intermittent hypoxic apnea compared with baseline (P < 0.05). Both total MSNA and MSNA burst frequency remained elevated throughout the 180-min recovery period and were statistically different from time control subjects throughout this period (P < 0.05). Finally, MSNA during recovery from intermittent hypoxic apnea, hypercapnic hypoxia, and isocapnic hypoxia were not different (P = 0.50). Therefore, these data support the hypothesis that short-term exposure to intermittent hypoxic apnea results in sustained elevation of MSNA and that hypoxia is the primary mediator of this response.     

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.     

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.     

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.     

Evidence of sustained forearm vasodilatation after brief isocapnic hypoxia.

Healthy subjects exposed to 20 min of hypoxia increase ventilation and muscle sympathetic nerve activity (MSNA). After return to normoxia, although ventilation returns to baseline, MSNA remains elevated for up to an hour. Because forearm vascular resistance is not elevated after hypoxic exposure, we speculated that the increased MSNA might be a compensatory response to sustained release of endogenous vasodilators. We studied the effect of isocapnic hypoxia (mean arterial oxygen saturation 81.6 +/- 4.1%, end-tidal Pco2 44.7 +/- 6.3 Torr) on plethysmographic forearm blood flow (FBF) in eight healthy volunteers while infusing intra-arterial phentolamine to block local alpha-receptors. The dominant arm served as control. Forearm arterial vascular resistance (FVR) was calculated as the mean arterial pressure (MAP)-to-FBF ratio. MAP, heart rate (HR), and FVR were reported at 5-min intervals at baseline, then while infusing phentolamine during room air, isocapnic hypoxia, and recovery. Despite increases in HR during hypoxia, there was no change in MAP throughout the study. By design, FVR decreased during phentolamine infusion. Hypoxia further decreased FVR in both forearms. With continued phentolamine infusion, FVR after termination of the exposure (17.47 +/- 6.3 mmHg x min x ml(-1) x 100 ml of tissue) remained lower than preexposure baseline value (23.05 +/- 8.51 mmHg x min x ml(-1) x 100 ml of tissue; P < 0.05). We conclude that, unmasked by phentolamine, the vasodilation occurring during hypoxia persists for at least 30 min after the stimulus. This vasodilation may contribute to the sustained MSNA rise observed after hypoxia.     

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.     

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.     

Chemoreflex and metaboreflex control during static hypoxic exercise

To investigate the effects of muscle metaboreceptor activation during hypoxic static exercise, we recorded muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, ventilation, and blood lactate in 13 healthy subjects (22 +/- 2 yr) during 3 min of three randomized interventions: isocapnic hypoxia (10% O(2)) (chemoreflex activation), isometric handgrip exercise in normoxia (metaboreflex activation), and isometric handgrip exercise during isocapnic hypoxia (concomitant metaboreflex and chemoreflex activation). Each intervention was followed by a forearm circulatory arrest to allow persistent metaboreflex activation in the absence of exercise and chemoreflex activation. Handgrip increased blood pressure, MSNA, heart rate, ventilation, and lactate (all P < 0.001). Hypoxia without handgrip increased MSNA, heart rate, and ventilation (all P < 0.001), but it did not change blood pressure and lactate. Handgrip enhanced blood pressure, heart rate, MSNA, and ventilation responses to hypoxia (all P < 0.05). During circulatory arrest after handgrip in hypoxia, heart rate returned promptly to baseline values, whereas ventilation decreased but remained elevated (P < 0.05). In contrast, MSNA, blood pressure, and lactate returned to baseline values during circulatory arrest after hypoxia without exercise but remained markedly increased after handgrip in hypoxia (P < 0.05). We conclude that metaboreceptors and chemoreceptors exert differential effects on the cardiorespiratory and sympathetic responses during exercise in hypoxia.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Daytime blood pressure elevation after nocturnal hypoxia.

The purpose of this study was to investigate whether nocturnal hypoxia causes daytime blood pressure (BP) elevation. We hypothesized that overnight exposure to hypoxia leads the next morning to elevation in BP that outlasts the hypoxia stimulus. We studied the effect on BP of two consecutive night exposures to hypobaric hypoxia in 10 healthy normotensive subjects. During the hypoxia nights, subjects slept for 8 h in a hypobaric chamber at a simulated altitude of 4,000 m (barometric pressure = 462 mmHg). Arterial O(2) saturation and electrocardiogram were monitored throughout the night. For 30 min before the nocturnal simulated ascent and for 4 h after return to baseline altitude the next morning, BP was measured every 5 min while the subject was awake. The same measurements were made before and after 2 normoxic nights of sleep in the hypobaric chamber at ambient barometric pressure (745 mmHg). Principal components analysis was applied to evaluate patterns of BP response after the second night of hypoxia and normoxia. A distinct pattern of diastolic BP (DBP) elevation was observed after the hypoxia night in 9 of the 10 subjects but in none after the normoxia night. This pattern showed a mean increase of 4 mmHg in DBP compared with the presleep-awake baseline in the first 60 min and a return to baseline by 90 min. We conclude that nocturnal hypoxia leads to a carryover elevation of daytime DBP.     

Carotid baroreflex function during and following voluntary apnea in humans

Muscle sympathetic nerve activity (MSNA) and arterial pressure increase concomitantly during apnea, suggesting a possible overriding of arterial baroreflex inhibitory input to sympathoregulatory centers by apnea-induced excitatory mechanisms. Apnea termination is accompanied by strong sympathoinhibition while arterial pressure remains elevated. Therefore, we hypothesized that the sensitivity of carotid baroreflex control of MSNA would decrease during apnea and return upon apnea termination. MSNA and heart rate responses to -60-Torr neck suction (NS) were evaluated during baseline and throughout apnea. Responses to +30-Torr neck pressure (NP) were evaluated during baseline and throughout 1 min postapnea. Apnea did not affect the sympathoinhibitory or bradycardic response to NS (P > 0.05); however, whereas the cardiac response to NP was maintained postapnea, the sympathoexcitatory response was reduced for 50 s (P < 0.05). These data demonstrate that the sensitivity of carotid baroreflex control of MSNA is not attenuated during apnea. We propose a transient rightward and upward resetting of the carotid baroreflex-MSNA function curve during apnea and that return of the function curve to, or more likely beyond, baseline (i.e., a downward and leftward shift) upon apnea termination may importantly contribute to the reduced sympathoexcitatory response to NP.     

Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects (P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.     

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.     

Hypoxia potentiates exercise-induced sympathetic neural activation in humans.

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.     

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

Systemic hemodynamics, including forearm blood flow and ventilatory parameters, were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic hypoxia. To evaluate the role of sympathetic nervous system activation in the changes, in 10 of these subjects, we measured muscle sympathetic nerve activity (MSNA) before and after exposure, and the remaining 11 subjects received intra-arterial phentolamine infusion in the brachial artery to define vascular tone in the absence of sympathetically mediated vasoconstriction. Short-term ventilatory acclimatization occurred as evidenced by a decrease in resting Pco(2) (from 42 +/- 1.4 to 37 +/- 0.96 mmHg) and by an increase in the slope of the ventilatory response to acute hypoxia [from 0.7 +/- 0.1 to 1.2 +/- 0.2 l.min(-1).%Sp(O(2)) (blood O(2) saturation from pulse oximetry)] after exposure. Subjects demonstrated a significant increase in resting heart rate (from 61 +/- 2 to 65 +/- 2 beats/min) and diastolic blood pressure (from 64.8 +/- 2.7 to 70.4 +/- 2.0 mmHg). MSNA did not change significantly after exposure, although there was a trend toward a decrease in burst frequency (from 19.8 +/- 4.1 to 14.3 +/- 1.2 bursts/min). Forearm vascular resistance showed a significant decrease after termination of exposure (from 37.7 +/- 3.6 to 27.6 +/- 2.7 mmHg.ml(-1).min.100 g tissue, P < 0.05). Initially, progressive isocapnic hypoxia elicited significant vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute challenge failed to change forearm vascular resistance. Local alpha-blockade with phentolamine restored the vasodilatory response to acute hypoxia in the postexposure setting.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Periods of intermittent hypoxic apnea can alter chemoreflex control of sympathetic nerve activity in humans

Obstructive sleep apnea is associated with sustained elevation of muscle sympathetic nerve activity (MSNA) and altered chemoreflex control of MSNA, both of which likely play an important role in the development of hypertension in these patients. Additionally, short-term exposure to intermittent hypoxic apneas can produce a sustained elevation of MSNA. Therefore, we tested the hypothesis that 20 min of intermittent hypoxic apneas can alter chemoreflex control of MSNA. Twenty-one subjects were randomly assigned to one of three groups (hypoxic apnea, hypercapnic hypoxia, and isocapnic hypoxia). Subjects were exposed to 30 s of the perturbation every minute for 20 min. Chemoreflex control of MSNA was assessed during baseline, 1 min posttreatment, and every 15 min throughout 180 min of recovery by the MSNA response to a single hypoxic apnea. Recovery hypoxic apneas were matched to a baseline hypoxic apnea with a similar nadir oxygen saturation. A significant main effect for chemoreflex control of MSNA was observed after 20 min of intermittent hypoxic apneas (P <0.001). The MSNA response to a single hypoxic apnea was attenuated 1 min postexposure compared with baseline (P <0.001), became augmented within 30 min of recovery, and remained augmented through 165 min of recovery (P <0.05). Comparison of treatment groups revealed no differences in the chemoreflex control of MSNA during recovery (P=0.69). These data support the hypothesis that 20 min of intermittent hypoxic apneas can alter chemoreflex control of MSNA. Furthermore, this response appears to be mediated by hypoxia.     

Influence of plasma osmolality on baroreflex control of sympathetic activity

The purpose of this study was to determine if plasma osmolality alters baroreflex control of sympathetic activity when controlling for a change in intravascular volume; we hypothesized that baroreflex control of sympathetic activity would be greater during a hyperosmotic stimulus compared with an isoosmotic stimulus when intravascular volume expansion was matched. Seven healthy subjects (25 +/- 2 yr) completed two intravenous infusions: a hypertonic saline infusion (HSI; 3% NaCl) and, on a separate occasion, an isotonic saline infusion (ISO; 0.9% NaCl), both at a rate of 0.15 ml x kg(-1) x min(-1). To isolate the effect of osmolality, comparisons between HSI and ISO conditions were retrospectively matched based on hematocrit; therefore, baroreflex control of sympathetic outflow was determined at 20 min of a HSI and 40 min of an ISO. Muscle sympathetic outflow (MSNA) was directly measured using the technique of peroneal microneurography; osmolality and blood pressure (Finometer) were assessed. The baroreflex control of sympathetic outflow was estimated by calculating the slope of the relationship between MSNA and diastolic blood pressure during controlled breathing. Plasma osmolality was greater during the HSI compared with the ISO (HSI: 292 +/- 0.9 mosmol/kg and ISO: 289 +/- 0.8 mosmol/kg, P < 0.05). Hematocrits were matched (HSI: 39.1 +/- 1% and ISO: 39.1 +/- 1%, P > 0.40); thus, we were successful in isolating osmolality. The baroreflex control of sympathetic outflow was greater during the HSI compared with the ISO (HSI: -8.3 +/- 1.2 arbitrary units x beat(-1) x mmHg(-1) vs. ISO: -4.0 +/- 0.8 arbitrary units x beat(-1) x mmHg(-1), P = 0.01). In conclusion, when controlling for intravascular volume, increased plasma osmolality enhances baroreflex control of sympathetic activity in humans.     

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans

We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.