Arterial Baroreflex Control Of Muscle Sympathetic Nerve Activity Research Articles

Abstract 13228: Cannabis Inhalation Reduces Muscle Sympathetic Nerve Activity in Humans

Introduction: Despite widespread use, the neuro-cardiovascular responses associated with cannabis use remain incompletely understood. Acute increases in heart rate, which are abolished under beta-adrenoreceptor blockade, suggest cannabis increases cardiac sympathetic activity; however, its effects on peripheral sympathetic outflow have not been measured. The objective of this work was to quantify direct recordings of efferent post-ganglionic muscle sympathetic nerve activity (MSNA) following cannabis inhalation. Hypothesis: MSNA would be increased following cannabis inhalation. Methods: Blood pressure (BP), heart rate, and MSNA measured from the fibular nerve, were recorded in seventeen young, healthy participants (22±3y: 8F) for a 10-minute epoch before and after inhalation of aerosolized dry cannabis flower (100mg, 13.6% THC). Cardiac output was estimated from finger photoplethysmography (Modelflow method). Arterial baroreflex control of MSNA was quantified using the slope of the weighted linear regression between diastolic BP and MSNA. Results: Mean BP (79±7 vs. 84±8mmHg), heart rate (61±7 vs. 81±14bpm), cardiac output (4.8±1.1 vs. 6.8±2.5L/min), and total vascular conductance (50±11 vs. 71±26mL/min/mmHg) were increased, while MSNA burst frequency (17±7 vs. 8±6bursts/min), incidence (29±11 vs. 11±9bursts/100hb), and amplitude (38.6±6.4% vs. 23.8±8.3%), and sympathetic baroreflex sensitivity (-3.9±1.8 vs. -1.5±1.5bursts/100hb/mmHg) were decreased following cannabis inhalation (all P <0.01). The rise in cardiac output was negatively associated with the reduction in MSNA burst frequency (r 2 =0.40; P <0.01). Conclusions: These data demonstrate that MSNA is reduced following acute cannabis inhalation in humans and is mediated, in part, through a baroreflex mechanism.

Stretching our understanding of baroreflex control in humans: evidence of a positive feedback pulmonary baroreflex.

Stretching our understanding of baroreflex control in humans: evidence of a positive feedback pulmonary baroreflex.

Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Hypoxia, a potent activator of the sympathetic nervous system, is known to increase muscle sympathetic nerve activity (MSNA) to the peripheral vasculature of native Lowlanders during sustained high altitude (HA) exposure. We show that the arterial baroreflex control of MSNA functions normally in healthy Lowlanders at HA, and that upward baroreflex resetting permits chronic activation of basal sympathetic vasomotor activity under this condition. The baroreflex MSNA operating point and resting sympathetic vasomotor outflow both are lower for highland Sherpa compared to acclimatizing Lowlanders; these lower levels may represent beneficial hypoxic adaptation in Sherpa. Acute hyperoxia at HA had minimal effect on baroreflex control of MSNA in Lowlanders and Sherpa, raising the possibility that mechanisms other than peripheral chemoreflex activation contribute to vascular sympathetic baroreflex resetting and sympathoexcitation. These findings provide a better understanding of sympathetic nervous system activation and the control of blood pressure during the physiological stress of sustained HA hypoxia. Exposure to high altitude (HA) is characterized by heightened muscle sympathetic neural activity (MSNA); however, the effect on arterial baroreflex control of MSNA is unknown. Furthermore, arterial baroreflex control at HA may be influenced by genotypic and phenotypic differences between lowland and highland natives. Fourteen Lowlanders (12 male) and nine male Sherpa underwent haemodynamic and sympathetic neural assessment at low altitude (Lowlanders, low altitude; 344m, Sherpa, Kathmandu; 1400m) and following gradual ascent to 5050m. Beat-by-beat haemodynamics (photoplethysmography) and MSNA (microneurography) were recorded lying supine. Indices of vascular sympathetic baroreflex function were determined from the relationship of diastolic blood pressure (DBP) and corresponding MSNA at rest (i.e. DBP 'operating pressure' and MSNA 'operating point'), as well as during a modified Oxford baroreflex test (i.e. 'gain'). Operating pressure and gain were unchanged for Lowlanders during HA exposure; however, the operating point was reset upwards (48±16vs. 22±12 bursts 100HB-1 ,P=0.001). Compared to Lowlanders at 5050m, Sherpa had similar gain and operating pressure, although the operating point was lower (30±13 bursts 100HB-1 , P=0.02); MSNA burst frequency was lower for Sherpa (22±11 vs. 30±9 bursts min-1 P=0.03). Breathing 100% oxygen did not alter vascular sympathetic baroreflex function for either group at HA. For Lowlanders, upward baroreflex resetting promotes heightened sympathetic vasoconstrictor activity and maintains blood pressure stability, at least during early HA exposure; mechanisms other than peripheral chemoreflex activation could be involved. Sherpa adaptation appears to favour a lower sympathetic vasoconstrictor activity compared to Lowlanders for blood pressure homeostasis.

Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy young humans.

What is the central question of this study? Water drinking increases muscle sympathetic nerve activity (MSNA), and it increases arterial blood pressure (ABP) in older populations but not in young healthy subjects. Does an increase in gain of arterial baroreflex control of MSNA contribute to maintenance of ABP after water drinking in healthy young subjects? What is the main finding and its importance? The gain of arterial baroreflex control of MSNA was increased and remained elevated 60min after water drinking (500ml) but remained unchanged after saline intake. An enhancement in gain of arterial baroreflex control of MSNA contributes to the maintenance of ABP after water drinking in young healthy subjects, probably via osmosensitive mechanisms. Water drinking increases muscle sympathetic nerve activity (MSNA), which is accompanied by a profound pressor response in patients with impaired arterial baroreflex function and in older populations, but not in healthy young subjects. We tested the hypothesis that an enhancement in the gain of arterial baroreflex control of MSNA contributes to the maintenance of arterial blood pressure after water drinking in healthy young subjects. The MSNA, arterial blood pressure and heart rate were measured in 10 healthy men (24± 2 years old; mean ± SD) before and for 60min after ingestion of 500ml of bottled water or saline solution. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. After water drinking, MSNA was significantly elevated within 15min and remained above baseline for up to 60min [e.g. 21± 10bursts (100heart beats)-1 mmHg-1 at baseline versus 35± 14 bursts (100heart beats)-1 mmHg-1 at 30min; P< 0.01], whereas mean arterial blood pressure (e.g. 87± 7mmHg at baseline versus 89± 7mmHg at 30min; P= 0.34) and heart rate were unchanged. The arterial baroreflex-MSNA gain for bursts incidence was increased and remained elevated throughout the protocol [e.g. -2.25± 0.99bursts (100heart beats)-1 mmHg-1 at baseline versus -4.32± 1.53 bursts (100heart beats)-1 mmHg-1 at 30min; P< 0.01]. Importantly, saline intake had no effect on arterial baroreflex-MSNA gain or any neurocardiovascular variables. These findings demonstrate that water drinking enhances the gain of arterial baroreflex control of MSNA in healthy young men, which may contribute to buffering the pressor response after water drinking, probably via osmosensitive mechanisms.

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.

Exercise training and hypocaloric diet improves sympathetic arterial baroreflex control in patients with metabolic syndrome and obstructive sleep apnea

Metabolic syndrome (MetS) decreases arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA). And, the obstructive sleep apnea (OSA) exacerbates this autonomic dysfunction. We tested the hypothesis that exercise training and hypocaloric diet (ET+D) would restore ABRMSNA in patients with MetS and OSA. Forty‐four MetS patients were allocated into four groups: Sedentary with OSA (MetS+OSA Sed, n=10) or without OSA (MetS‐OSA Sed, n=10), and ET+D with OSA (MetS+OSA ET+D, n=11) or without OSA (MetS‐OSA ET+D, n=13). The ET+D groups were submitted to −500 kcal/day and 40 min bicycle exercise for 4‐months. OSA was deferred as apnea‐hypopnea index&gt;;15 events/hour. MSNA (microneurography), blood pressure (beat‐to‐beat, noninvasive) and spontaneous ABRMSNA (gain, sensitivity and time delay, latency) were evaluated. ET+D decreased MSNA (P&lt;0.05) and increased ABRMSNA gain in both MetS+OSA (13±1 vs. 24±2 ms/mmHg, P=0.01) and MetS‐OSA (27±3 vs. 37±3ms/mmHg, P=0.03) groups. The time delay of ABRMSNA was reduced by ET+D only in MetS+OSA group (4.1±0.2 vs. 2.8±0.3 s, P=0.04). No changes were observed in the sedentary groups. In conclusion, the ET+D improve ABRMSNA sensitivity in patients with MetS regardless of OSA. However, this effect of ET+D is more pronounced in patients with MetS+OSA.Support: CNPq and FAPESP#2011/17533–6

Arterial baroreflex control of sympathetic nerve activity during acute hypotension is enhanced in young normotensive black men

Although impairments in arterial baroreflex (ABR) control of heart rate have been reported in black compared to white subjects, no studies have examined the potential for racial differences in the ABR control of muscle sympathetic nerve activity (MSNA). Therefore, we tested the hypothesis that ABR control of MSNA is impaired in young black men compared to white men. In 12 non‐hypertensive men (7 black and 5 white, age 18–27 yr) ABR control of MSNA was determined using 100μg i.v. of sodium nitroprusside (NTP) followed 1 min later by 150μg of phenylephrine (PE) during supine rest (3 trials/subject). The slope of the relationship (i.e., gain) between changes in diastolic blood pressure and MSNA was determined. Overall sympathetic baroreflex gain was not different between racial groups (blacks: − 1.9±0.2 vs. whites: −2.4 ± 0.4 AU·beat·mmHg−1, p&gt;;0.05). Similarly, sympathetic baroreflex gain for hypertension (PE phase) was also not different between groups (blacks: −1.9±0.3 vs. whites: −1.7±0.2 AU·beat·mmHg−1, p&gt;;0.05). However, sympathetic baroreflex gain for hypotension (NTP phase) was significantly elevated in blacks (−4.0±0.3) compared to whites (−3.2±0.1 AU·beat·mmHg−1, p&lt;0.05). In contrast to our hypothesis, these preliminary findings suggest that ABR control of MSNA is similar or enhanced in young blacks compared to their white counterparts.Supported by NIH Grant R15HL096103 (DMK) and RO1 HL093167 (PJF)

Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS - OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS - OSA (P < 0.01) and C (P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS - OSA (P < 0.001 and P < 0.01, respectively) and C (P < 0.001 and P < 0.001, respectively). Patients with MetS - OSA showed decreased oscillatory pattern of MSNA compared with C (P < 0.01). The sensitivity of the ABRMSNA was lower in MetS - OSA than in C group (P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.

Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans

Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (34 ± 6 uIU ml(1); P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: 3.29 ± 0.54 baseline vs. 5.64 ± 0.67 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (42 ± 6 μIU ml(1); P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: 2.44 ± 0.29 baseline vs. 4.74 ± 0.71 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA.

Insulin‐mediated increases in arterial baroreflex control of muscle sympathetic nerve activity following meal intake in humans

Animal studies indicate that insulin enhances arterial baroreflex (ABR) control of sympathetic nerve activity (SNA); however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, we utilized a mixed meal as a physiological method to evoke sustained increases in plasma insulin. Muscle SNA and arterial blood pressure (BP) were measured in 10 subjects (25 ± 2 yr) before and for 120 minutes following mixed meal intake. Weighted linear regression analysis between muscle SNA and diastolic BP was used to determine the gain (i.e. sensitivity) of ABR control of SNA. Plasma insulin was significantly elevated within 30 minutes following meal intake (Δ29 ± 7 uIU; P&lt;0.05) and remained above baseline for up to 120 minutes. Similarly, 30 minutes after meal intake, ABR gain of muscle SNA burst incidence (−3.31 ± 0.64 vs. −5.13 ± 0.95 bursts/100 heart beats/mmHg; baseline vs. 30 min, P&lt;0.05) and total muscle SNA (−3.22 ± 0.60 vs. −5.89 ± 1.30 arbitrary units/beat/mmHg; baseline vs. 30 min, P&lt;0.05) was increased and remained elevated for the duration of the protocol. BP was unchanged by meal intake. In a subset of subjects the ABR muscle SNA gain remained unchanged during time control experiments. These preliminary findings suggest that increases in plasma insulin following meal intake enhance the gain of ABR control of muscle SNA in healthy humans.Support: NIH RO1HL093167

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans

The relationship between muscle sympathetic nerve activity (MSNA) and diastolic blood pressure has been used to describe two sites for arterial baroreflex control of MSNA. By determining both the likelihood of occurrence for sympathetic bursts and the area of each burst for a given diastolic blood pressure, both a 'gating' and an 'area' control site has been described in normothermic humans. Assessing the effect of heat stress on these mechanisms will improve the understanding of baroreflex control of arterial blood pressure under this thermal condition. Therefore, the purpose of this study was to test the hypothesis that heat stress enhances arterial baroreflex control of burst gating and area. In 10 normotensive subjects (age, 32+/-2 years; mean+/-s.e.m.), MSNA (peroneal) was assessed using standard microneurographic techniques. Five minute periods of data were examined during normothermic and whole-body heating conditions. The burst incidence (i.e. number of sympathetic bursts per 100 cardiac cycles) and the area of each burst were determined for each cardiac cycle and were placed into 3 mmHg intervals of diastolic blood pressure. During normotheric conditions, there was a moderate, negative relationship between burst incidence and diastolic blood pressure (slope=-2.49+/-0.38; r(2)=0.73+/-0.06; mean+/-s.e.m.), while area per burst relative to diastolic blood pressure exhibited a less strong relationship (slope=-1.13+/-0.46; r(2)=0.45+/-0.09). During whole-body heating there was an increase in the slope of the relationship between burst incidence and diastolic blood pressure (slope=-4.69+/-0.44; r(2)=0.84+/-0.03) compared to normothermia (P<0.05), while the relationship between area per burst and diastolic blood pressure was unchanged (slope=-0.92+/-0.29; r(2)=0.41+/-0.08) (P=0.50). The primary finding of this investigation is that, at rest, whole-body heating enhanced arterial baroreflex control of MSNA through increased sensitivity of a 'gating' mechanism, as indicated by an increase in the slope of the relationship between burst incidence and diastolic blood pressure. This occurrence is likely to afford protection against potential decreases in arterial blood pressure in an effort to preserve orthostatic tolerance during heat stress.

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

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

Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation

Large, reproducible interindividual differences exist in resting sympathetic nerve activity among normotensive humans with similar arterial pressures, resulting in a lack of correlation between muscle sympathetic nerve activity (MSNA) and arterial pressure among individuals. Although it is known that the arterial pressure is the main short-term determinant of MSNA in humans via the arterial baroreflex, the lack of correlation among individuals suggests that the level of arterial pressure is not the only important input in regulation of MSNA in humans. We studied the relationship between cardiac output (CO) and baroreflex control of sympathetic activity by measuring MSNA (peroneal microneurography), arterial pressure (arterial catheter), CO (acetylene uptake technique) and heart rate (HR; electrocardiogram) in 17 healthy young men during 20 min of supine rest. Across individuals, MSNA did not correlate with mean or diastolic blood pressure (r<0.01 for both), but displayed a significant negative correlation with CO (r=-0.71, P=0.001). To assess whether CO is related to arterial baroreflex control of MSNA, we constructed a baroreflex threshold diagram for each individual by plotting the percentage occurrence of a sympathetic burst against diastolic pressure. The mid-point of the diagram (T50) at which 50% of cardiac cycles are associated with bursts, was inversely related to CO (r=-0.75, P<0.001) and stroke volume (SV) (r=-0.57, P=0.015). We conclude that dynamic inputs from CO and SV are important in regulation of baroreflex control of MSNA in healthy, normotensive humans. This results in a balance between CO and sympathetically mediated vasoconstriction that may contribute importantly to normal regulation of arterial pressure in humans.

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

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

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.

The sympathetic nervous system and hypertension: recent developments.

A major hypothesisfor the development of hypertension is that abnormal renal excretory function is critical for the initiation, development, and maintenance of primary hypertension.1 The renal body fluid feedback mechanism couples the long-term regulation of arterial pressure to extracellular volume (sodium and water) homeostasis via pressure natriuresis, whereby the kidneys respond to changes in arterial pressure by altering urinary sodium and water excretion. The obligatory requirement for maintenance of sodium and water balance by the kidneys is believed to be primary in the long-term control of arterial pressure. An increase in arterial pressure (via increases in total peripheral resistance or cardiac output or both) leads to an increased urinary sodium and water excretion via the pressure natriuresis mechanism, with consequent reduction in blood volume until arterial pressure is returned to normal. Thus, factors that decrease renal excretory function and disrupt the maintenance of sodium and water balance by the kidneys lead to an increase in arterial pressure, which is required to reestablish and maintain sodium and water balance. Based on computer modeling studies, a long-term increase in arterial pressure can only occur if there is a chronic and sustained decrease in renal excretory function. Increased renal sympathetic nerve activity (RSNA) is known to be a factor capable of decreasing renal excretory function.2,3 The renal effects of increased RSNA include increased renal tubular sodium reabsorption leading to renal sodium retention; decreased renal blood flow and glomerular filtration rate with renal vasoconstriction and increased renal vascular resistance; and increased renin release leading to angiotensin II production. Each of these renal functional alterations can decrease renal excretory function. The role of increased RSNA as being a critically important factor contributing to this renal excretory dysfunction in hypertension is strengthened by the fact that increased RSNA has been identified in hypertensive human …

Sympathetic and cardiac baroreflex function in panic disorder.

Recent reports have demonstrated increased cardiac risk, and an association with essential hypertension in patients with panic disorder. The cause is not known, but possibly involves sympathetic nervous activation. In this study, we evaluated the arterial baroreflex control of vascular sympathetic nervous outflow and cardiac baroreflex function in panic disorder patients. We studied nine patients suffering from panic disorder and ten healthy subjects. Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of blood pressure (BP) and electrocardiogram (ECG). The relationship between MSNA and spontaneous diastolic BP (DBP) changes was assessed at rest and was defined as the arterial baroreflex control of MSNA. Cardiac baroreflex function was assessed using the sequence method. Anxiety was assessed using Spielberger's anxiety state and trait inventory. The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001). Panic disorder patients had significantly higher state and trait anxiety scores. The slope of the relationship between MSNA and diastolic BP was significantly related to the trait anxiety of the subjects. There was no difference between the cardiac baroreflex sensitivity between the two groups. Patients with panic disorder exhibit enhanced reflex gain of the arterial baroreflex control of MSNA but no change in the cardiac baroreflex. While any clinical significance this observation might have in relation to increased cardiac risk in panic disorder, or to concordance with essential hypertension, remains to be elucidated, increased reactivity of vasoconstricting sympathetic nerves may be a trait characteristic in this cohort.

Two sites for modulation of human sympathetic activity by arterial baroreceptors?

1. Peroneal muscle sympathetic nerve activity (MSA), finger blood pressure and cardiac intervals were recorded at rest in 60 healthy subjects, aged 18-71 years. Arterial baroreflex control of MSA was analysed by relating each spontaneous sympathetic burst to the diastolic blood pressure and the cardiac interval of the heart beat during which the burst was generated. The results were expressed as blood pressure/cardiac interval threshold for occurrence of bursts, and as baroreflex sensitivity (i.e. the relationship between diastolic pressure/cardiac interval and burst strength). 2. Significant blood pressure/cardiac interval thresholds were present in all subjects and old subjects had less variability of thresholds than young subjects. In contrast, significant baroreflex sensitivity for diastolic pressure and cardiac interval was present in only 55 and 73 % of the subjects, respectively. There was no age-related difference in sensitivity. 3. In 40 subjects, two 5 min periods from the same recording were analysed. The number of sympathetic bursts and the threshold for occurrence of bursts were reproducible in all subjects. In contrast, significant baroreflex sensitivity in both periods was present in only 30 % (diastolic pressure) and 40 % (cardiac interval) of the subjects. 4. The results show that the baroreflex mechanisms regulating the occurrence and strength of sympathetic bursts are not identical. We suggest that the modulation occurs at two sites, one which determines whether or not a burst will occur, and another at which the strength of the discharge is determined.

Baroreflex control of muscle sympathetic nerve activity in mild hypertension

The importance of the arterial baroreflex control of muscle sympathetic nerve activity (MSNA) has been investigated in physiological conditions and in cardiovascular dysfunctions. However, there is no consensus about the role played by the MSNA in hypertensive states, probably due to the diversity of the methods used to study the arterial baroreflex control of MSNA. In the present study we evaluated the reflex changes in MSNA by increasing and decreasing the mean arterial pressure (MAP) through 1 min intravenous infusion of phenylephrine (1 μg/kg) and sodium nitroprusside (1 μg/kg), respectively, in eight normotesive and eight mild hypertesive subjects. Both MAP and MSNA were significantly higher in hypertensive (117 ± 2 mm Hg and 30 ± 3 bursts/min) than in normotensive (96 ± 4 mm Hg and 20 ± 3 bursts/min) subjects. The reflex gain was calculated by the ratio percent of changes in MSNA/percent changes in MAP. The maximal reflex gain was statistically similar in normotensive and hypertensive groups during phenylephrine (5.1 ± 1.4 ν 4.3 ± 0.4 bursts/mm Hg, respectively) and nitroprusside (10.7 ± 2.3 ν 8.1 ± 1.3 bursts/mm Hg, respectively) infusion. The present data showing that arterial baroreflex control of MSNA is not depressed in hypertensive subjects indicate that the elevated basal MSNA and the mild hypertension in human beings is not a consequence of baroreflex control of MSNA dysfunction.