Autonomic dysfunction in children with sleep-disordered breathing

STUDY OBJECTIVES: To measure sympathetic responses in children with and without sleep-disordered breathing. DESIGN: Prospective, observational study. SETTING: Kosair Children's Hospital Sleep Medicine and Apnea Center. PARTICIPANTS: Subjects were prospectively recruited from children undergoing overnight polysomnographic assessments and were retrospectively grouped according to the results of the polysomnogram. Sleep-disordered breathing was defined as an apnea-hypopnea index >5 and children were assigned to the control group if their apnea-hypopnea index was < 1. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: During quiet wakefulness, pulse arterial tonometry was used to assess changes in sympathetic activity following vital capacity sighs in 28 children with sleep-disordered breathing and 29 controls. Each child underwent a series of 3 sighs, and the average maximal pulse arterial tonometry signal attenuation was calculated. Further, a cold pressor test was conducted in a subset of 14 children with sleep-disordered breathing and 14 controls. The left hand was immersed in ice cold water for 30 seconds while right-hand pulse arterial tonometry signal was continuously monitored during immersion and 20-minute recovery periods. Signal amplitude changes were expressed as percentage change from corresponding baseline. Results: The magnitude of sympathetic discharge-induced attenuation of pulse arterial tonometry signal was significantly increased in children with sleep-disordered breathing during sigh maneuvers (74.1% +/- 10.7% change compared with 59.2% +/- 13.2% change in controls; P<.0001) and the cold pressor test (83.5% +/- 7.3% change compared with 74.1% +/- 11.4% change in controls; P=.039). Further, recovery kinetics in control children were faster than those of children with sleep-disordered breathing. CONCLUSION: Children with sleep-disordered breathing have altered autonomic nervous system regulation as evidenced by increased sympathetic vascular reactivity during wakefulness.     

Influence of arterial baroreceptors and intracerebroventricular guanabenz on synchronized renal nerve activity

The contributions of changes in the number of active fibres and the peak interval of synchronized neural discharges to arterial baroreflex regulated alterations in renal sympathetic nerve activity were examined in intact conscious rats. Stimulation of central nervous system α₂ adrenoreceptors with intracerebroventricular guanabenz (10, 20, 40 μg) was used to alter renal sympathetic nerve activity by a non-reflex mechanism in both intact and sinoaortic denervated (SAD) rats. Synchronized renal sympathetic nerve discharge was analysed with the sympathetic peak detection algorithm. When arterial pressure was increased from 50 mmHg to 150 mmHg in intact rats, the peak height (number of simultaneously active fibres) of synchronized discharges decreased in a sigmoidal fashion while the peak interval remained unchanged. Guanabenz produced a dose dependent inhibition of renal sympathetic nerve activity due to both a decrease in peak height and an increase in peak interval of synchronized discharges in both intact and SAD rats. Arterial baroreflex mediated changes in renal sympathetic nerve activity are due to changes in the number of simultaneously active nerve fibres. Central nervous system α₂ adrenoreceptor stimulation decreases renal sympathetic nerve activity by decreasing the number of active fibres and increasing the peak interval, acting on additional neural pathways not involved in buffering acute arterial pressure changes.     

Secretory immunoglobulin A and cardiovascular activity during mental arithmetic and paced breathing.

The role of the autonomic nervous system in secretory immunoglobulin A (sIgA) responses to laboratory challenge was explored in a study in which sIgA and cardiovascular activity were recorded at rest and during mental arithmetic and paced breathing. These tasks were selected to preferentially engage the sympathetic and parasympathetic nervous systems, respectively. Mental arithmetic elicited a mixed pattern of increased alpha- and beta-adrenergic activity and a reduction in parasympathetic activity; diastolic blood pressure, total peripheral resistance, and systolic blood pressure increased, preejection period shortened, and heart rate variability decreased. In contrast, paced breathing primarily elicited an increase in parasympathetic activity; heart rate variability increased. Mental arithmetic also provoked an increase in sIgA concentration but no change in saliva volume, whereas paced breathing affected neither sIgA concentration nor saliva volume. These data suggest that sIgA responses to laboratory challenges are mediated by sympathetic rather than parasympathetic processes.     

Sympathetic nerve activity in obstructive sleep apnoea

The mechanisms underlying the link between obstructive sleep apnoea (OSA) and cardiovascular disease are not completely established. However, there is increasing evidence that autonomic mechanisms are implicated. A number of studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic. During sleep, repetitive episodes of hypoxia, hypercapnia and obstructive apnoea act through chemoreceptor reflexes and other mechanisms to increase sympathetic drive. Remarkably, the high sympathetic drive is present even during daytime wakefulness when subjects are breathing normally and no evidence of hypoxia or chemoreflex activation is apparent. Several neural and humoral mechanisms may contribute to maintenance of higher sympathetic activity and blood pressure. These mechanisms include chemoreflex and baroreflex dysfunction, altered cardiovascular variability, vasoconstrictor effects of nocturnal endothelin release and endothelial dysfunction. Long-term continuous positive airway pressure treatment decreases muscle sympathetic nerve activity in OSA patients. The vast majority of OSA patients remain undiagnosed. Unrecognized OSA may contribute, in part, to the metabolic and cardiovascular derangements that are thought to be linked to obesity, and to the association between obesity and cardiovascular risk. Furthermore, acting through sympathetic neural mechanisms, OSA may contribute to or augment elevated levels of blood pressure in a large proportion of the hypertensive patient population.     

Sympathetic nerve activity in hypotension and orthostatic intolerance

AIM: The present paper reviews how changes in sympathetic nerve activity are related to hypotensive episodes and orthostatic intolerance in humans. RESULTS: It has been well documented that sympathetic neural traffic to skeletal muscles (muscle sympathetic nerve activity; MSNA) plays an essential role in maintaining blood pressure homeostasis mainly through baroreflex. The MSNA responded to gravitational loading from the head to the leg (+Gz) during passive head-up tilt (HUT). Patients who suffered from orthostatic hypotension with or without syncope were classified into at least two groups; low and high responders of MSNA to orthostatic loading. The typical examples belonging to the former group were patients of multiple system atrophy who had very low basal sympathetic outflow to muscle which responded extremely poorly to HUT. Patients of multiple system atrophy presented also postprandial hypotension in which muscle sympathetic response to oral glucose administration was absent. The latter group was represented by subjects who manifested vasovagal syncope with normal or even higher muscle sympathetic response to HUT, which was suddenly withdrawn concomitantly with bradycardia and hypotension. Similar withdrawal of sympathetic nerve traffic to muscle was encountered in a rare case of idiopathic non-orthostatic episodic hypotension which accompanied bradycardia. The MSNA was suppressed by short-term exposure to microgravity but was enhanced after long-term exposure to microgravity. Orthostatic intolerance after long-term exposure to microgravity was related to progressive reduction of muscle sympathetic response to orthostatic loading with impaired arterial baroreflex. CONCLUSION: It is concluded that hypotensive episodes are closely related to poor or lack of muscle sympathetic outflow, but may depend on various neural mechanisms to induce it.     

Dominance in cardiac parasympathetic activity during real recreational SCUBA diving

It was already established that exposure to hyperbaric conditions induces vagal-depended bradycardia but field study on autonomic nervous system (ANS) activity during self-contained underwater breathing apparatus (SCUBA) diving is lacking. The aim of the present study was to evaluate ANS modifications during real recreational SCUBA diving using heart rate variability analysis (timedomain, frequency-domain and Poincaré plot) in 10 experienced and volunteers recreational divers. Mean RR, root mean square of successive differences of interval (rMSSD), high frequency of spectral analysis and standard deviation 1 of Poincaré Plot increased (P < 0.05) during dive. Low frequency/high frequency ratio decreased during dive (P < 0.05) but increased after (P < 0.05). Recreational SCUBA diving induced a rise in vagal activity and a decrease in cardiac sympathetic activity. Conversely, sympathetic activity increases (P < 0.05) during the recovery.     

The reproducibility of power spectrum analysis of heart rate variability before and after a standardized meal

We tested the reproducibility of the heart rate variability (HRV) measurements before and after a standardized meal. Heart rate recordings were obtained in 14 healthy subjects tested in a reclining position before and after a standardized meal on two separated occasions, apart by a 1-2-week interval. We measured three components of HRV: sympathetic activity (SYMP), parasympathetic activity (PSYMP) and the ratio of SYMP/PSYMP under controlled breathing and noncontrolled breathing conditions. We observed that all components were reproducible during noncontrolled breathing condition, whereas only PSYMP was reproducible during controlled breathing condition. Our results thus indicate that HRV measurements could be a useful, noninvasive and nonexpensive method to provide SYMP and SYMP/PSYMP in feeding behavior studies when measured under noncontrolled breathing conditions. Nonetheless, using a controlled breathing condition may be relevant when assessing the effect of various interventions or drugs on parasympathetic activity.     

Low ambient temperature increases baroreflex-governed sympathetic outflow to muscle vessels in humans

Microelectrode multi-unit recordings of muscle nerve sympathetic activity, primarily involved in blood pressure regulation, were made from the right peroneal nerve in 10 healthy subjects during exposure to cold inside a box used for hypothermic surgery. Blood pressure was monitored by an automatic cuff applied to the left arm. Heart activity (ECG) and the temperature inside the box were monitored. Muscle nerve sympathetic activity outflow and blood pressure were stable during 15 minutes initial rest at 22.7 +/- 0.3 degrees C (mean +/- SEM). All subjects increased muscle nerve sympathetic activity and blood pressure with lowering of ambient temperature. The box temperature was 10.5 +/- 0.3 degrees C at the end of the cooling period. With rewarming the changes in muscle nerve sympathetic activity and blood pressure were reversed. Mean outflows of muscle nerve sympathetic activity during initial rest, final phase of cooling period, and post-rewarming were 20.3 +/- 2.7, 26.6 +/- 3.2 and 20.2 +/- 2.8 burst min-1, respectively. Systolic blood pressure during the same periods was 118 +/- 3, 131 +/- 4 and 120 +/- 4 mmHg, respectively, whereas corresponding values for diastolic blood pressure were 73 +/- 2, 82 +/- 2 and 75 +/- 2 mmHg (P less than 0.001 for all variables; (ANOVA). It is concluded that muscle nerve sympathetic activity, while not regarded as being involved in body temperature regulation, is under the influence of ambient temperature and contributes to blood pressure elevation in a cold environment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The "Senobi" breathing exercise ameliorates depression in obese women through up-regulation of sympathetic nerve activity and hormone secretion

Obese individuals have an increased risk of developing depression. This study aimed to determine whether the "Senobi" breathing exercise (SBE), a stretching-breathing exercise that we have established, could relieve depression, especially in obese women. Forty premenopausal women, aged 40 to 49 years, participated in the present study. Twenty were healthy, and the other 20 were obese (body mass index > 25 and body fat > 30%) and in a depressive state (OWD). Sympathetic nerve activity determined by analyzing heart rate variability, and the hormone levels in the urine were investigated before and 30 min after one minute of SBE. The relative proportion of sympathetic nerve activity among healthy women in the daytime was 79.2 ± 2.3%, whereas that in OWD group was 30.4 ± 1.9%. After one minute of SBE, significant up-regulation of sympathetic nerve activity and increased concentrations of catecholamines, estradiol, and growth hormone (all P values < 0.001) were observed in OWD group. After 30 days of SBE, the sympathetic nerve activity and hormone levels had recovered in OWD group, and the depressive state, as evaluated by the Hamilton Depression Scale, had ameliorated. The "Senobi" breathing exercise was found to be effective for amelioration of depression in obese women possibly through up-regulation of sympathetic nerve activity and hormone secretion.     

Sympathetic nerve activity in metabolic control – some basic concepts

A role for the sympathetic nervous system in hypertension has been looked for in relation to the ‘metabolic syndrome’ with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin‐induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2‐deoxy‐d ‐glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change. After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C‐peptide‐negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure. A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipous tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the ‘metabolic syndrome’ and hypertension.     

Peripheral Chemoreflex and Baroreflex Interactions in Cardiovascular Regulation in Humans

We tested the hypothesis that activation of peripheral chemoreceptors with acute isocapnic hypoxia resets arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow to higher pressures, resulting in increased heart rate and muscle sympathetic nerve activity without changes in baroreflex sensitivity. We further hypothesized that this resetting would not occur during isocapnic hyperpnoea at the same breathing rate and depth as during isocapnic hypoxia. In 12 healthy, non-smoking, normotensive subjects (6 women, 6 men, 19-36 years), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity using the modified Oxford technique during normoxia, isocapnic hyperpnoea, and isocapnic hypoxia (85 % arterial O₂ saturation). While isocapnic hyperpnoea did not alter heart rate, arterial pressure, or sympathetic outflow, hypoxia increased heart rate from 61.9 ± 1.8 to 74.7 ± 2.7 beats min⁻¹ (   P < 0.05  ), increased mean arterial pressure from 97.4 ± 2.0 to 103.9 ± 3.3 mmHg (   P < 0.05  ), and increased sympathetic activity 22 ± 13 % relative to normoxia and 72 ± 21 % (   P < 0.05  ) relative to hyperpnoea alone. The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by either hypoxia or hyperpnoea. Thus, it appears that acute activation of peripheral chemoreceptors with isocapnic hypoxia resets baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity. Furthermore, these effects appear largely independent of breathing rate and tidal volume.     

Cyclic intermittent hypoxia enhances renal sympathetic response to ICV ET-1 in conscious rats

To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague–Dawley rats to CIH or to room air sham (Sham) for 8 h/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8 ± 15.6% of baseline; Sham 112.2 ± 10.0% of baseline; CIH vs. Sham, P = 0.0373). This enhanced sympathetic response to i.c.v. ET-1 was associated with greater expression of endothelin receptor A (ETA) protein in the subfornical organs of CIH-exposed relative to Sham-exposed rats. We conclude that 3-week CIH exposure enhances central ET-1 receptor expression and the sympathetic response to i.c.v. ET-1 suggesting central endothelin may contribute to the sympathetic and hemodynamic response to cyclic intermittent hypoxia.     

去心交感神经对QT离散度的影响

目的：采用动物实验方法，观察去心交感神经对QT离散度（QTd）的影响，并观察QT离散度的昼夜节律变化，以探讨QT离散度变化的电生理基础。 方法： 以新西兰兔作为实验对象，实验组手术去除心交感神经支配，对照组手术保留心交感神经支配。观察两组手术前后QTd变化及24 h内QTd的昼夜变化。 结果： 实验组在手术后QTd显著减小(P＜0.05)，对照组在手术前后QTd无显著变化（P＞0.05）；实验组在手术后24 h内QTd始终低于对应的对照组，且无明显节律变化，对照组在24 h内QTd呈现出显著的昼夜节律变化。 结论： 心交感神经活动可能是产生QTd的机制之一。     

Haptoglobin phenotype, sleep-disordered breathing, and the prevalence of cardiovascular disease: the Sleep Heart Health Study

BACKGROUND: Diabetes is an independent risk factor for cardiovascular disease, and there is growing evidence that sleep-disordered breathing also may increase the risk of cardiovascular disease. The mechanism responsible for increased susceptibility of people with diabetes to cardiovascular disease is thought to share several features with sleep-disordered breathing, notably increased oxidative stress. We recently demonstrated that a particular haptoglobin phenotype that is associated with differential antioxidant activity is an independent risk factor for cardiovascular disease in individuals with diabetes. We therefore sought to determine whether sleep-disordered breathing and cardiovascular disease are more strongly associated among people with the unfavorable haptoglobin phenotype. METHODS: We tested this hypothesis in 2612 middle-aged and older participants from the Sleep Heart Health Study. Haptoglobin phenotyping was performed by gel electrophoresis. Respiratory disturbance index was assessed by standard methods. Logistic regression analysis was performed to estimate the association between haptoglobin phenotype and cardiovascular disease, adjusting for known cardiovascular risk factors (age, sex, diabetes, smoking, lipid levels, and hypertension). Possible modification by haptoglobin phenotype of the association of sleep-disordered breathing with cardiovascular disease prevalence was explored by examining interaction terms. RESULTS: We found no significant association between haptoglobin phenotype and prevalent cardiovascular disease in this cohort, nor were significant interactions found between haptoglobin phenotype and sleep-disordered breathing on the prevalence of cardiovascular disease. CONCLUSIONS: Sleep-disordered breathing did not appear to interact with haptoglobin phenotype in modifying the association with prevalent cardiovascular disease in the Sleep Heart Health Study. These findings could be due to the absence of association or to survivor bias in these cross-sectional analyses.     

Dream recall frequency and nightmare frequency in patients with sleep-disordered breathing

Question of the study

There are conflicting findings regarding dream recall frequency (DRF) in patients with sleep-disordered breathing: Various studies have reported less, equal, or higher DRF in comparison with healthy controls. Although more negatively toned dreams were found in these patients, nightmare frequency had not been found to be increased in a previous study. This study concerned whether DRF or nightmare frequency was altered in patients with sleep-disordered breathing without other comorbid diagnoses and whether disorder-related parameters, comorbidity, or drug intake was associated with DRF and nightmare frequency.

Patients and methods

The present study assessed home DRF and nightmare frequency via two rating scales in 1,706 patients with sleep-disordered breathing. These data were compared with those of healthy control samples from other studies.

Results

In comparison with the control group, a reduced DRF was found that was not associated with respiratory parameters or comorbidity. Similarly, nightmare frequency was reduced, and one might speculate whether these findings can be explained by cognitive dysfunction, which is often found in patients with sleep-disordered breathing. Use of antidepressants and psychiatric comorbidity were associated with heightened nightmare frequency.

Conclusions

Future studies should include current medication intake, measures of cognitive functioning, and sleep parameters in order to explain reduced DRF and reduced nightmare frequency in patients with sleep-disordered breathing.     

Cardiac autonomic characteristics in infants sleeping with their head covered by bedclothes

The risk of Sudden Infant Death Syndrome is increased in infants sleeping with their head covered by bedding items. This study was designed to evaluate cardiac autonomic nervous controls in infants sleeping with the head covered by bedclothes. Sixteen healthy infants with a median age of 12 weeks (range 9-13 weeks) were recorded polygraphically for one night. While they slept in their usual supine position, a bedsheet was placed over their head for about 45 min. All infants were challenged with the head covered and with the head free during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Sleep, breathing and heart rate (HR) characteristics were recorded simultaneously, together with rectal and pericephalic temperatures. In both head-free and head-covered conditions, autoregressive spectral analysis of HR was evaluated as a function of sleep stages. During the head-covered periods, parasympathetic tonus decreased and sympathetic activity increased in both REM and NREM sleep. Compared with the head-free periods, the head-covered sleep periods were characterized by greater rectal (P = 0.012) and pericephalic temperatures (P = 0.002). Covering the infant's head with a bedsheet was associated with significant changes in autonomic balance. The finding could be related to an elevation in temperatures within the infant's microenvironment.     

The Effects of Different Noise Types on Heart Rate Variability in Men

Purpose

To determine the impact of noise on heart rate variability (HRV) in men, with a focus on the noise type rather than on noise intensity.

Materials and Methods

Forty college-going male volunteers were enrolled in this study and were randomly divided into four groups according to the type of noise they were exposed to: background, traffic, speech, or mixed (traffic and speech) noise. All groups except the background group (35 dB) were exposed to 45 dB sound pressure levels. We collected data on age, smoking status, alcohol consumption, and disease status from responses to self-reported questionnaires and medical examinations. We also measured HRV parameters and blood pressure levels before and after exposure to noise. The HRV parameters were evaluated while patients remained seated for 5 minutes, and frequency and time domain analyses were then performed.

Results

After noise exposure, only the speech noise group showed a reduced low frequency (LF) value, reflecting the activity of both the sympathetic and parasympathetic nervous systems. The low-to-high frequency (LF/HF) ratio, which reflected the activity of the autonomic nervous system (ANS), became more stable, decreasing from 5.21 to 1.37; however, this change was not statistically significant.

Conclusion

These results indicate that 45 dB(A) of noise, 10 dB(A) higher than background noise, affects the ANS. Additionally, the impact on HRV activity might differ according to the noise quality. Further studies will be required to ascertain the role of noise type.     

Middle cerebral artery blood velocity,arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia

During exercise the transcranial Doppler determined mean blood velocity (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 ± 20 to 92 ± 21 beats min^?1 and mean arterial pressure (MAP) from 87 ± 7 to 105 ± 9 mmHg (mean ± SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 ± 9 mmHg). During handgrip contralateral MCA V_mean increased from 65 ± 10 to 75 ± 13 cm s^?1 and this was more than on the ipsilateral side (from 63 ± 10 to 68 ± 10 cm s^?1; P < 0.05). On both sides of the brain V_mean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 ± 24 to 116 ± 39 units) but the elevation became statistically significant during PEMI (135 ± 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, V_mean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.     

Reflex responses evoked in the adrenal sympathetic nerve to electrical stimulation of somatic afferent nerves in the rat

The present study was initiated to determine the role of somatic A (myelinated) and C (unmyelinated) afferent fibers in both responses of increases and decreases in adrenal sympathetic nerve activities during repetitive mechanical pinching and brushing stimulations of the skin in anesthetized rats with central nervous system (CNS) intact. Accordingly, changes in adrenal sympathetic nerve activity resulting from repetitive and single shock electrical stimulation of various spinal afferent nerves, especially the 13th thoracic (Th13) spinal nerve and the sural nerve, were examined in urethane/chloralose-anesthetized rats. Repetitive electrical stimulation of A afferent fibers in Th13 spinal or sural nerve decreased the adrenal nerve activity similarly as brushing stimulation of skin of the lower chest or hindlimb did, while repetitive stimulation of A plus C afferent fibers of those nerves increased the adrenal nerve activity as pinching stimulation of those skins did. Single shock stimulation of spinal afferent nerves evoked various reflex components in the adrenal nerve: an initial depression of spontaneous activity (the early depression); the following reflex discharge due to activation of A afferent fibers (the A-reflex); a subsequent reflex discharge due to activation of C afferent fibers (the C-reflex); and following post-excitatory depressions. These reflexes seem to be mediated mainly via supraspinal pathways since they were abolished by spinal transection at the C1-2 level. Although the supraspinal A- and C-reflexes could be elicited from stimulation of a wide variety of spinal segmental afferent levels, the early depression was more prominent when afferents at spinal segments closer to the level of adrenal nerve outflow were excited. It is suggested that the decreased responses of the adrenal nerve during repetitive electrical stimulation of A afferent nerve fibers are attributable to summation of both the early depression and post-excitatory depression evoked by single shock stimulation, while the increased responses during repetitive stimulation of A plus C afferent fibers are attributable to summation of the C-reflex after single shock stimulation. In spinalized rats, repetitive stimulation of Th13 always increased the adrenal nerve activities regardless of whether A fibers alone or A plus C fibers were stimulated, just as brushing and pinching of the lower chest skin always increased them. The increased responses in spinal animals seem to be related to the fact that single electrical stimuli of Th13 produced A- and C-reflexes of spinal origin without clear depressions.     

Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans

We raised and lowered arterial pressures with stepwise intravenous infusions of phenylephrine and nitroprusside in ten healthy young men and measured changes of R-R intervals, post-ganglionic peroneal nerve muscle sympathetic activity, and antecubital vein plasma noradrenaline and neuropeptide Y concentrations. Respiratory peak-valley R-R interval changes declined with arterial pressure reductions, but did not rise with pressure elevations. Sympathetic activity was modulated by respiration over the entire range of pressures and, at each pressure, was more prominent in expiration than inspiration. Levels of muscle sympathetic nerve activity were low during supine rest, were suppressed almost completely during small increases of pressure, and were increased proportionally during pressure reductions. Over a range of average diastolic pressures from 69 to 89 mmHg, antecubital vein plasma noradrenaline levels were related linearly (r = 0.86, P = 0.0001) to muscle sympathetic nerve activity. Neuropeptide Y levels increased proportionally with muscle sympathetic nerve activity during pressure reductions, but did not decline during pressure elevations. Our results suggest that in man, muscle sympathetic outflow is modulated finely by small changes of baroreceptor input, and that during pharmacologically induced changes of arterial pressure, changes of antecubital vein plasma noradrenaline concentrations provide excellent estimates of changes of sympathetic nerve traffic to skeletal muscle.