The current study tested the hypothesis that modification in central hemodynamics during short-term continuous positive airway pressure (CPAP) application was accompanied by altered firing patterns of sympathetic nerve activity in CHF patients and healthy subjects.
Muscle sympathetic nerve activity (MSNA), hemodynamic and ventilatory parameters were obtained from 8 healthy middle aged subjects and 7 CHF patients. Action potentials (APs) were extracted from MSNA neurograms, quantified as AP frequency and classified into different sized clusters. While on CPAP at 10 cm H2O, multi-unit MSNA, AP frequency and mean burst area/min increased in healthy middle aged subjects (p < 0.05) whereas CPAP had no effect on these variables in CHF patients. In conclusion, the impact of CPAP on central hemodynamics in healthy individuals elicited a moderate activation of sympathetic neurons through increased AP firing frequency, whereas in CHF patients both hemodynamics and MSNA remained unaltered.
Action potential detection; Microneurography; End-expiratory positive pressure; Human
End-expiratory breath-holds (BH) and Mueller manoeuvres (MM) elicit large increases in muscle sympathetic nerve activity (MSNA). In 16 healthy humans (9♀, 35±4 years) we used functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast to determine the cortical network associated with such sympathoexcitation. We hypothesized that increases in MSNA evoked by these simulated apneas are accompanied by BOLD contrast changes in the insular cortex, thalamus and limbic cortex. A series of 150 whole-brain images were collected during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg). The identical protocol was repeated separately with MSNA recorded from the fibular nerve. The time course of the sympathoexcitatory response to both breathing tasks were correlated with whole-brain BOLD signal changes. Brain sites demonstrating both positive (activation) and negative (deactivation) correlations with the MSNA time course were identified. Sympathetic burst incidence increased (p<0.001) from 29±6 (rest) to 49±6 (BH) and 47±6 bursts/100 heartbeats (MM). Increased neural activity (Z-scores) was identified in the right posterior and anterior insular cortices (3.74, 3.64), dorsal anterior cingulate (3.42), fastigial and dentate cerebellar nuclei (3.02, 3.34). Signal intensity decreased in the left posterior insula (3.28) and ventral anterior cingulate (3.01). Apnea both activates and inhibits elements of a cortical network involved in the generation of sympathetic outflow. These findings identify a neuroanatomical substrate to guide future investigations into central mechanisms contributing to disorders characterized by elevated basal MSNA and exaggerated sympathetic responses to simulated apneas such as sleep apnea and heart failure.
Although the β1-adrenergic blocking agent atenolol is an established antihypertensive therapy, its effect on peripheral sympathetic vasoconstrictor drive has remained controversial. In patients with hypertension, atenolol therapy has been reported to either increase or have no effect on peripheral vascular resistance, despite other reports showing no change or a decrease in peripheral sympathetic drive. This study was designed, in patients with untreated essential hypertension (EHT), to quantify changes in simultaneously measured peroneal muscle sympathetic nerve activity (MSNA) and calf vascular resistance (CVR) accompanying atenolol therapy. MSNA was quantified as the mean frequency of single units (s-MSNA) and as multiunit bursts (MSNA bursts) using the technique of microneurography, and CVR was measured using a standard plethysmographic technique. Firstly, by comparing two age- and body weight-matched groups, each of 14 patients with hypertension, we found that the group on atenolol therapy (treated-HT) had similar MSNA values counted over the same number of cardiac beats and similar CVR levels (at least P>0.40) to the group without therapy (untreated-HT). Secondly, we examined 10 EHT patients before and after 8±0.4 weeks of oral atenolol therapy (HT-A) in comparison to seven control patients with hypertension and no treatment (HT-C) who were examined over a similar period of time. We found that the measures of MSNA and CVR did not significantly change in both groups. We conclude that the arterial pressure lowering effect of atenolol was not related to significant changes in central vasoconstrictor sympathetic drive to the periphery.
antihypertensive therapy; sympathetic nervous system; hypertension, essential; vascular resistance
The cardiovascular and respiratory effects of exercise have been widely studied, as have the autonomic effects of imagined and observed exercise. However, the effects of observed exercise in the first person have not been documented, nor have direct recordings of muscle sympathetic nerve activity (MSNA) been obtained during observed or imagined exercise. The aim of the current study was to measure blood pressure, heart rate, respiration, skin blood flow, sweat release, and MSNA (via microelectrodes inserted into the common peroneal nerve), during observation of exercise from the first person point of view. It was hypothesized that the moving stimuli would produce robust compensatory increases in the above-mentioned parameters as effectively as those generated by mental imagery and—to a lesser extent—actual exercise. Nine subjects watched a first-person running video, allowing them to view the action from the perspective of the runner rather than viewing someone else perform the exercise. On average, statistically significant increases from baseline during the running phase were seen in heart rate, respiratory rate, skin blood flow, and burst amplitude of MSNA. These results suggest that observation of exercise in the first person is a strong enough stimulus to evoke “physiologically appropriate” autonomic responses that have a purely psychogenic origin.
autonomic nervous system; muscle sympathetic nerve activity; cardiovascular; exercise; microneurography
Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.
sympathetic nerve activity; heart failure; exercise; arrhythmia
The influence of the ovarian cycle on muscle sympathetic nerve activity (MSNA) remains controversial. Some studies report an increase of resting MSNA during the midluteal (ML) phase of the ovarian cycle compared to the early follicular phase (EF), while others do not. These inconsistent findings may be due, in part, to the variable surges in estradiol and/or progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE2) and progesterone (ΔP). Multiple regression analysis of data from previous studies with complete recordings of mean arterial pressure (MAP), MSNA, E2, and P during both EF and ML phases were available from 30 eumenorrheic women (age, 28±1 yr; BMI, 23±0 kg/m2). ML phase increased E2 (37±2 to 117±9 pg/ml; p<.001), P (1±0 to 11±1 ng/ml; p<.001), and MSNA (12±1 to 15±1 bursts/min; p=.02), but did not alter MAP (83±2 to 83±2 mmHg; p=.91). ΔMSNA was correlated to ΔE2 (r=−.50, p=.003) and ΔE2/ΔP (r=−.52, p=.002), but not ΔP (r=.21, p=.13). There was no association between ΔMAP and ΔE2 (r=−.13, p=.49), ΔP (r=−.04, p=.83), or ΔE2/ΔP (r<.01, p=.98). In conclusion, sympathoexcitation during the ML phase of the ovarian cycle appears to be dependent, in part, upon the degree of sex steroid surges. This dynamic interaction between E2, P, and MSNA likely explains previously reported inconsistencies in the field; it remains possible that other sex steroids, such as testosterone, might explain further variance.
menstrual cycle; autonomic activity; microneurography; blood pressure
We used phosphorus nuclear magnetic resonance spectroscopy (31P-NMR) to probe the cellular events in contracting muscle that initiate the reflex stimulation of sympathetic outflow during exercise. In conscious humans, we performed 31P-NMR on exercising forearm muscle and simultaneously recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve to determine if the activation of MSNA is coupled to muscle pH, an index of glycolysis, or to the concentrations (II) of inorganic phosphate (Pi) and adenosine diphosphate (ADP) which are modulators of mitochondrial respiration. During both static and rhythmic handgrip, the onset of sympathetic activation in resting muscle coincided with the development of cellular acidification in active muscle. Furthermore, increases in MSNA were correlated closely with decreases in intracellular pH but dissociated from changes in phosphocreatine [( PCr]), [Pi], and [ADP]. The principal new conclusion is that activation of muscle sympathetic outflow during exercise in humans is coupled to the cellular accumulation of protons in contracting muscle.
During static exercise, heart failure (HF) subjects activate the sympathetic nervous system differently than normal controls. HF causes metaboreceptor desensitization with either enhanced mechanoreceptor activity or central command. In this report, we examined whether increased muscle interstitial pressure, as seen in HF, augments other neural systems. We measured muscle sympathetic nerve activity (MSNA; peroneal nerve) in 10 normals during static exercise (40% maximal voluntary grip) and posthandgrip circulatory arrest (PHG-CA). This was repeated after venous congestion (VC; cuff inflation to 90 mmHg). VC increased forearm volume (plethysmography) by 4.7%. MSNA responses to exercise were greater after VC (150.5 +/- 41.8 vs. 317.3 +/- 69.9 arbitrary units; P < 0.01). However, MSNA responses during PHG-CA were not affected by VC, and 31P nuclear magnetic resonance (n = 5) demonstrated no effect of VC on pH or H2PO4-. Similar effects of VC on MSNA were noted after ischemic exercise (n = 7), excluding flow alterations as the explantation. VC probably sensitized mechanically sensitive afferents since MSNA during involuntary biceps contractions increased after VC (n = 6), and skin sympathetic nerve responses during handgrip, an index of central command, were not increased by VC (n = 6).
Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are two diseases that often coexist within an individual. This coexistence is known as overlap syndrome and is the result of chance rather than a pathophysiological link. Although there are claims of a very high incidence of OSAS in COPD patients, recent studies report that it is similar to the general population. Overlap patients present sleep-disordered breathing associated to upper and lower airway obstruction and a reduction in respiratory drive. These patients present unique characteristics, which set them apart from either COPD or OSAS patients. COPD and OSAS are independent risk factors for cardiovascular events and their coexistence in overlap syndrome probably increases this risk. The mechanisms underlying cardiovascular risk are still unclear, but may involve systemic inflammation, endothelial dysfunction, and tonic elevation of sympathetic neural activity. The treatment of choice for overlap syndrome in stable patients is CPAP with supplemental oxygen for correction of upper airway obstructive episodes and hypoxemia during sleep.
chronic obstructive pulmonary disease; obstructive sleep apnea syndrome; overlap syndrome; sleep; cardiovascular disease
The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin-sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue.
We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in the leg during arm exercise in conscious humans to test the concept that central command and muscle afferent reflexes produce mass sympathetic discharge at the onset of exercise. Nonischemic rhythmic handgrip and mild arm cycling produced graded increases in heart rate and arterial pressure but did not increase MSNA, whereas ischemic handgrip and moderate arm cycling dramatically increased MSNA. There was a slow onset and offset of the MSNA responses, which suggested metaboreceptor mediation. When forearm ischemia was continued after ischemic handgrip, MSNA remained elevated (muscle chemoreflex stimulation) but heart rate returned to control (elimination of central command). The major new conclusions are that: the onset of dynamic exercise does not produce mass, uniform sympathetic discharge in humans, and muscle chemoreflexes and central command appear to produce differential effects on sympathetic and parasympathetic responses.
Static exercise in normal humans causes reflex increases in muscle sympathetic nerve activity (MSNA) that are closely coupled to the contraction-induced decrease in muscle cell pH, an index of glycogen degradation and glycolytic flux. To determine if sympathetic activation is attenuated when muscle glycogenolysis is blocked due to myophosphorylase deficiency (McArdle's disease), an inborn enzymatic defect localized to skeletal muscle, we now have performed microelectrode recordings of MSNA in four patients with McArdle's disease during static handgrip contraction. A level of static handgrip that more than doubled MSNA in normal humans had no effect on MSNA and caused an attenuated rise in blood pressure in the patients with myophosphorylase deficiency. In contrast, two nonexercise sympathetic stimuli, Valsalva's maneuver and cold pressor stimulation, evoked comparably large increases in MSNA in patients and normals. The principal new conclusion is that defective glycogen degradation in human skeletal muscle is associated with a specific reflex impairment in sympathetic activation during static exercise.
The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity's effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate (HR) are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR) and cardiopulmonary stretch receptors (cardiopulmonary baroreflex). In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA) while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure, and HR responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of mean arterial blood pressure (MAP) and greater HR response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.
sympathetic nervous system; lower body negative pressure; integrated circulatory regulation; blood pressure; peripheral reflexes
Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO2) in HF relates inversely to MSNA at rest and during exercise.
To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO2) that is augmented in HF.
MSNA at rest and VE/VCO2 during stationary cycling were measured in 30 patients (27 men) with HF (mean ± SD ejection fraction 20±6%) and in 31 age-matched controls (29 men).
MSNA was higher in HF patients than in controls (51.5±14.3 bursts/min versus 33.0±11.1 bursts/min; P<0.0001). The VE/VCO2 slope was also higher in HF patients than in controls (33.7±5.7 versus 26.0±3.5; P<0.0001), whereas pVO2 was lower in HF patients than in controls (18.6±6.6 versus 31.4±8.4 mL/kg/min; P<0.0001). There were significant relationships between MSNA and VE/VCO2 in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 × MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO2, identified a significant independent relationship between MSNA burst frequency and VE/VCO2 (P=0.013) that differed between HF and controls (P<0.01).
The magnitude of resting sympathetic activity correlates positively with the VE/VCO2 slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.
Chronic heart failure; Sympathetic nervous system; Ventilation
Increased (central) sympathetic activity is a key feature of heart failure and associated with worse prognosis. Animal studies suggest that statin therapy can reduce central sympathetic outflow. This study assessed statin effects on (central) sympathetic activity in human chronic heart failure (CHF) patients.
Sympathetic activity was measured in eight patients with CHF patients during 8 weeks after discontinuation and 4 weeks after restart of statin therapy by microneurography for direct muscle sympathetic nerve recording (MSNA) and measurement of arterial plasma norepinephrine concentrations.
During discontinuation of statin therapy, MSNA was significantly increased (73 ± 4 vs. 56 ± 5 and 52 ± 6 bursts/100 beats, p = 0.01). Burst frequency was significantly higher after statin discontinuation (42 ± 3 burst/min without statin vs. 32 ± 3 and 28 ± 3 burst/min during statin therapy, p = 0.004). Mean normalized burst amplitude and total normalized MSNA were significantly higher after statin discontinuation (mean normalized burst amplitude 0.36 ± 0.04 without statin vs. 0.29 ± 0.04 and 0.22 ± 0.04 during statin, p < 0.05; total normalized MSNA 15.70 ± 2.78 without statin, vs. 9.28 ± 1.41 and 6.56 ± 1.83 during statin, p = 0.009). Arterial plasma norepinephrine levels and blood pressure were unaffected.
Statin therapy inhibits central sympathetic outflow in CHF patients, as measured by MSNA.
Heart failure; Nervous system, sympathetic; Statin; Catecholamines; HRV
Objective: To clarify the characteristics of sympathetic vasomotor function in Parkinson's disease by sympathetic neurographic analysis.
Methods: Muscle sympathetic nerve activity (MSNA) was recorded using a microneurographic technique at rest and during head up tilt in 18 patients with idiopathic Parkinson's disease and 21 healthy controls.
Results: Heart rate and blood pressure at rest did not differ between index and control subjects. The increase in these variables and MSNA in response to tilting was slightly blunted in the Parkinson's group. Resting MSNA showed a negative correlation with age in patients with Parkinson's disease (p<0.05) and a positive correlation with age in controls (p<0.01). There was a negative correlation between duration of disease or disability levels and MSNA (p<0.01).
Conclusions: Sympathetic vasomotor function may be related to age and disease duration in Parkinson's disease.
Following tilt-induced syncope, blood pressure usually recovers rapidly after tilt back to the horizontal position. However, in some patients, hemodynamic recovery is delayed, a condition recently termed “prolonged post-faint hypotension” (PPFH). The mechanism is thought to be mediated by increased vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have been reported in this condition, so we aimed to confirm that neither vasodilatation nor MSNA withdrawal was responsible.
To retrospectively select patients with satisfactory recordings of continuous BP and MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in patients with PPFH to patients with normal recovery (NR) after tilt-back.
All patients were studied in Christchurch, New Zealand, between 1998 and 2008 using continuous arterial BP monitoring, and microneurographic recordings of MSNA from the right leg. Only patients with satisfactory BP and MSNA data throughout baseline, head-up tilt and presyncope were selected. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived using Modelflow. After baseline measurements, patients were tilted to the head-up 60° position and given GTN spray if asymptomatic after 20 min. Following the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH was defined as systolic BP <85 mmHg for at least 2 min after tilt-back. Measurements were averaged at baseline, early tilt, presyncope, early and late recovery. Within-group comparisons were made between baseline and all other time points. Between-group comparisons were made over all time points.
Patients with PPFH (7 males, age 46 ± 5 years, n = 8) and with NR (8 males, age 47 ± 6 years, n = 8) were selected. Presyncope was provoked by GTN in 4/8 patients in each group. In both groups, MAP remained below baseline during early and late recovery: PPFH 84 ± 5 versus 51 ± 5 and 64 ± 5 mmHg (p = 0.001, p = 0.001); NR 104 ± 5 versus 83 ± 5 and 93 ± 5 mmHg (p = 0.001, p = 0.03). However, MAP and HR were lower in the PPFH group (p = 0.004, p = 0.023). During early recovery, CO remained below baseline only in the PPFH group (p = 0.001), whereas TPR remained constant in both groups. In both groups, all MSNA indices tended to remain above baseline levels during early and late recovery. PPFH 25 ± 2 increased to 31 ± 6 and 29 ± 4 bursts/min (p = 0.09, 0.02); NR 23 ± 3 increased to 33 ± 3 and 34 ± 3 bursts/min (p = 0.06, 0.01).
PPFH does not appear to be mediated by exaggerated vasodilatation or sympathetic withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a more likely mechanism.
Prolonged post faint hypotension (PPFH); Muscle sympathetic nerve activity (MSNA); Total peripheral resistance (TPR); Cardiac output (CO); Sympathetic withdrawal; Vagal outflow
Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients.
hemorrhage; sympathetic activity; MSNA; baroreflex function; central hypovolemia; LBNP
The menstrual cycle has been reported to alter mean arterial pressure (MAP), but not muscle sympathetic nerve activity (MSNA), during vestibular activation. Specifically, MAP responses to head-down rotation (HDR) are augmented during the midluteal (ML) phase compared to the early follicular (EF) phase in young, eumenorrheic women. The purpose of the present study was to determine if the menstrual cycle influences vestibular-mediated changes in limb blood flow. MSNA, MAP, heart rate, and limb blood flow responses to HDR were measured in 12 healthy women. Resting MSNA, MAP, heart rate, forearm blood flow and calf blood flow were not altered by the menstrual cycle. HDR elicited similar increases in MSNA during the EF (Δ3 ± 1 bursts/min; P < 0.05) and ML (Δ2 ± 1 bursts/min; P < 0.05) phase, but only increased MAP during the ML phase (Δ4 ± 2 mmHg; P < 0.05). HDR did not change heart rate during either the EF or ML phase. HDR elicited similar increases in calf vascular resistance during the EF (Δ6 ± 2 mmHg/mL/100mL/min; P < 0.05) and ML (Δ7 ± 2 mmHg/mL/100mL/min; P < 0.05) phases of the menstrual cycle. In contrast, HDR increased forearm vascular resistance during the ML phase (Δ4 ± 2 mmHg/mL/100mL/min; P<0.05), but not the EF phase (Δ0 ± 2 mmHg/mL/100mL/min). These findings suggest an increased transduction of sympathetic nerve activity into forearm vascular resistance during the ML phase, and reveal the first recorded divergent vascular response to vestibular excitation in human limbs.
Muscle sympathetic nerve activity; autonomic activity; arterial blood pressure; head-down rotation; estrogen
Overweight individuals (body mass index (BMI) 25–29.9 kg/m2) are at higher risk for developing cardiovascular disease and hypertension when compared with lean individuals of normal weight (BMI 18.5–24.9 kg/m2). The purpose of this study was to test the hypothesis that exaggerated sympathetic nervous system responses to stressors may be one potential mechanism that predisposes overweight individuals to developing hypertension.
We compared heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) using microneurography, in normotensive overweight individuals compared with age-matched lean controls, at baseline and during two sympathoexcitatory maneuvers: cold pressor test (CPT), and static handgrip exercise (SHG 30%).
During CPT, MSNA increased in both groups, but the magnitude of MSNA response was significantly greater (P = 0.03) in overweight (+18.1 ± 2.8 bursts/min) compared with lean controls (+10.8 ± 1.2 bursts/min). MSNA response to SHG at 30% maximum voluntary contraction (MVC) was similar between the two groups. There were no significant differences in systolic (SBP) or diastolic BP (DBP) responses or HR responses between the two groups during either maneuver.
Normotensive overweight individuals have an exaggerated MSNA response to the CPT. Augmented sympathetic reactivity to cold stress may contribute to increased risk of hypertension in overweight individuals.
blood pressure; hypertension; overweight; physiological stress response; sympathetic nervous system
Mental stress (MS) and changes in posture can both be associated with cardiovascular dysfunction. The purpose of this study was to determine neurovascular responses to MS in the supine and upright postures. MS was elicited in 17 subjects (26 ± 1 y) by 5 min of mental arithmetic. Doppler ultrasound was used to measure peak blood velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV). Leg blood flow (LBF) was measured using Doppler ultrasound and forearm blood flow (FBF) was measured using plethysmography. Microneurography was used to measure muscle sympathetic nerve activity (MSNA; n = 5) in the leg. At rest, heart rate and MSNA were significantly greater whereas LBF, FBF, RBFV, and SMBFV and their respective conductances were significantly less in the upright compared to supine posture. MS elicited similar increases in mean arterial pressure (~12 mmHg) and heart rate (~17 beats/min) regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not elicit changes in MSNA in either the supine or upright posture (~ Δ 2 ± 2 bursts/min and ~ Δ 1 ± 2 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial pressure, or MSNA responses to MS. MS elicits a divergent vascular response in the visceral and peripheral vasculature. These results indicate that although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.
visceral blood flow; sympathetic; orthostatic; vascular conductance; renal; forearm
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 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 ~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.
prostaglandins; exercise; nervous system; sympathetic; mechanoreceptor
Obstructive sleep apnea (OSA) is characterized by episodes of repeated airway obstruction resulting in cessation (apnea) or reduction (hypopnea) in airflow during sleep. These events lead to intermittent hypoxia and hypercapnia, sleep fragmentation, and changes in intrathoracic pressure, and are associated with a marked surge in sympathetic activity and an abrupt increase in blood pressure. Blood pressure remains elevated during wakefulness despite the absence of obstructive events resulting in a high prevalence of hypertension in patients with OSA. There is substantial evidence that suggests that chronic intermittent hypoxia (CIH) leads to sustained sympathoexcitation during the day and changes in vasculature resulting in hypertension in patients with OSA. Mechanisms of sympathoexcitation include augmentation of peripheral chemoreflex sensitivity and a direct effect on central sites of sympathetic regulation. Interestingly, the vascular changes that occur with CIH have been ascribed to the same molecules that have been implicated in the augmented sympathetic tone in CIH. This review will discuss the hypothesized molecular mechanisms involved in the development of hypertension with CIH, will build a conceptual model for the development of hypertension following CIH, and will propose a systems biology approach in further elucidating the relationship between CIH and the development of hypertension.
obstructive sleep apnea; hypertension; chronic intermittent hypoxia; sympathoexcitation; systems biology
Muscle passive contraction of lower limb by neuromuscular electrostimulation (NMES) is frequently used in chronic heart failure (CHF) patients but no data are available concerning its action on sympathetic activity. However, Transcutaneous Electrical Nerve Stimulation (TENS) is able to improve baroreflex in CHF. The primary aim of the present study was to investigate the acute effect of TENS and NMES compared to Sham stimulation on sympathetic overactivity as assessed by Muscle Sympathetic Nerve Activity (MSNA).
We performed a serie of two parallel, randomized, double blinded and sham controlled protocols in twenty-two CHF patients in New York Heart Association (NYHA) Class III. Half of them performed stimulation by TENS, and the others tested NMES.
Compare to Sham stimulation, both TENS and NMES are able to reduce MSNA (63.5 ± 3.5 vs 69.7 ± 3.1 bursts / min, p < 0.01 after TENS and 51.6 ± 3.3 vs 56.7 ± 3.3 bursts / min, p < 0, 01 after NMES). No variation of blood pressure, heart rate or respiratory parameters was observed after stimulation.
The results suggest that sensory stimulation of lower limbs by electrical device, either TENS or NMES, could inhibit sympathetic outflow directed to legs in CHF patients. These properties could benefits CHF patients and pave the way for a new non-pharmacological approach of CHF.
Obstructive sleep apnea (OSA) is increasingly being recognized as a major health burden with strong focus on the associated cardiovascular risk. Studies from the last two decades have provided strong evidence for a causal role of OSA in the development of systemic hypertension. The acute physiological changes that occur during apnea promote nocturnal hypertension and may lead to the development of sustained daytime hypertension via the pathways of sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. This review will focus on the acute hemodynamic disturbances and associated intermittent hypoxia that characterize OSA and the potential pathophysiological mechanisms responsible for the development of hypertension in OSA. In addition the epidemiology of OSA and hypertension, as well as the role of treatment of OSA, in improving blood pressure control will be examined.
obstructive sleep apnea; hypertension; intermittent hypoxia; ambulatory blood pressure; sympathetic activation