Control Of Sympathetic Nervous System Research Articles

Assessing and Comparing Multiple Metrics of Heart Rate Variability to Measure Cardiac Parasympathetic and Sympathetic Tone – Does the Math Miss a Beat?

The relative contributions of parasympathetic and sympathetic autonomic nervous system control of cardiac activity is often assessed through non-invasive heart rate variability (HRV) metrics. There are various HRV metrics utilized to measure cardiac autonomic balance. However, the relationship between HRV metrics and cardiac autonomic tone is understudied and controversial. We assessed the internal consistency of using three specific HRV metrics of cardiac autonomic balance at rest using electrocardiography (ECG) in a larger number of healthy participants: time domain, frequency domain and Poincaré plots. Data was analyzed from a large set (n=136) of archived files from previous studies, where a 5-min segment of resting baseline ECG was previously-recorded in young, healthy men and women (ADInstruments, LabChart HRV module, v8). The three specific HRV metrics quantified from the ECG baseline were time domain (SDRR and RMSSD; ms), frequency domain (LF, HF, LF/HF; n.u.) and Poincaré plots (SD1, SD2, SD1/SD2; ms). The HRV metrics considered to be associated with cardiac parasympathetic activity are RMSSD, HF and SD1, whereas SDRR, LF and SD2 are considered to be associated with mixed cardiac parasympathetic and sympathetic activity (i.e., sympathetic influence). We correlated the three parasympathetic HVR metrics (RMSSD, HF and SD1), within-individual. We also correlated the three mixed cardiac autonomic metrics (SDRR, LF and SD2), within-individual. Regarding the three parasympathetic metrics, (a) RMSSD and SD1 were strongly, positively and significantly-correlated (r=1.0, P<0.0001), suggesting similar mathematical calculations for each and (b) both RMSSD and HF, and SD1 and HF were moderately, positively and significantly-correlated (both, rs=0.41, P<0.00001). Regarding mixed parasympathetic and sympathetic metrics, (a) SDRR and SD2 were strongly, positively and significantly-correlated (r=0.96, P<0.0001), suggesting similar mathematical calculations for each, (b) SDRR and LF were not significantly-correlated (rs=-0.1, P=0.25) and (c) SD2 and LF were no significantly correlated (rs=0.01, P=0.9). Our analysis on a large data set suggests high agreement and internal consistency between parasympathetic cardiac metrics, within-individual. However, on metrics with mixed parasympathetic and sympathetic influence, HRV metrics lacked agreement and internal consistently. These data suggest that (a) any of the three parasympathetic metrics are likely useful in assessing cardiac parasympathetic tone, but that (b) caution should be used in interpreting HRV metrics typically utilized in assessing cardiac sympathetic tone.

The sympathetic muscle metaboreflex is not different in the third trimester in normotensive pregnant women.

Isometric handgrip (IHG) is used to assess sympathetic nervous system responses to exercise and may be useful at predicting hypertension in both pregnant and nonpregnant populations. We previously observed altered sympathetic nervous system control of blood pressure in late pregnancy. Therefore, we measured muscle sympathetic nerve activity (MSNA) and blood pressure during muscle metaboreflex activation (IHG) in normotensive pregnant women in the third trimester compared with in healthy nonpregnant women. Further, 19 pregnant (32 ± 3 wk gestation) and 14 nonpregnant women were matched for age, non/prepregnant body mass index (BMI), and parity. MSNA (microneurography), heart rate (ECG), and arterial blood pressure (Finometer) were continuously recorded during 10 min of rest, and then during 2 min of IHG at 30% of maximal voluntary contraction, and 2 min of postexercise circulatory occlusion (PECO). Baseline sympathetic nerve activity (SNA) was elevated in pregnant (41 ± 11 bursts/min) compared with nonpregnant women (27 ± 9 bursts/min; P = 0.005); however, the sympathetic baroreflex gain and neurovascular transduction were not different between groups (P = 0.62 and P = 0.32, respectively). During IHG and PECO, there were no significant differences in the pressor responses (ΔMAP) between groups, (P = 0.25, main effect of group) nor was the sympathetic response different between groups (interaction effect: P = 0.16, 0.25, and 0.27 for burst frequency, burst incidence, and total SNA, respectively). These data suggest that pregnant women who have maintained sympathetic baroreflex and neurovascular transduction also have similar sympathetic and pressor responses during exercise.NEW & NOTEWORTHY We compared sympathetic nervous system activation by muscle metaboreflex between pregnant women in the third trimester and nonpregnant women. We show that the sympathetic nerve activity and associated pressor responses to isometric handgrip and post-exercise circulatory occlusion are not different between third-trimester pregnant and nonpregnant women. These data suggest that unlike other reflexes (e.g., cold pressor test or head-up tilt), metaboreflex control is maintained in pregnant women.

Obesity‐Induced Sympathoexcitation is Associated with Glial Senescence in the Brainstem

Previous studies from our laboratory showed that high fat diet‐induced obesity causes cellular senescence in the key brainstem region, the rostral ventrolateral medulla which is critical for the tonic and reflex control of sympathetic nervous system. Cellular senescence is characterized by a state of irreversible growth arrest and senescence‐associated secretory phenotype (SASP) in proliferating cells. In the current study, we wanted to investigate which cell type undergoes senescence in the brainstem in obesity. Neurons are post‐mitotic and do not undergo senescence, whereas glial cells can undergo senescence. Hence we hypothesized that obesity induces glial senescence in the brainstem. To address this hypothesis, 2‐month old C57BL/6J mice were fed with high fat diet (60% fat; n=5) and chow diet (10% fat; n=5) for 16 weeks. The animals were sacrificed at the end of the experiment, and their brains were collected for further processing. The freshly isolated brainstem was enzymatically digested (45 minutes, 37°C) and filtered through a 30μm mesh to form a cell suspension. Neuron isolation kit from Miltenyi Biotec was used to isolate glial and neuronal enriched cell population from the brainstem. RNA was extracted from these sorted cells and used for RT‐PCR analysis. Senescence was assessed using gene expression of cell cycle inhibitors and SASP factors. Data was analyzed by unpaired student’s t‐test and a p‐value less than 0.05 was considered statistically significant. We observed an increase in the gene expression of cell cycle inhibitors, p21 and p53 in the glial cell fraction isolated from the brainstem of obese mice compared to its lean counterparts. In addition, there was an increase in the mRNA levels of SASP factors such as the IL‐6 and MCP1 suggesting that obesity induces glial senescence in the brainstem. We were not able to obtain viable neurons for senescence analysis. Glial cells are known to play a supporting role in neuronal function through regulation of neurotransmission. Future studies will address glial cell specific mechanisms and understand how glia‐neuron crosstalk contributes to sympathetic nerve overactivity in obesity.Support or Funding InformationNIH‐HL148844 and RED account funds

Sympathetic nervous system control of vascular function and blood pressure during pregnancy and preeclampsia.

: Proper vascular tone and blood pressure regulation during pregnancy are important for immediate and long-term cardiovascular health of the mother and her offspring. Preeclampsia is clinically defined as new-onset maternal hypertension accompanied by cardiovascular, renal, and/or neural abnormalities presenting in the second half of pregnancy. There is strong evidence to support that preeclampsia is mediated by attenuations in uteroplacental vascular remodeling and increases in vasoconstriction with subsequent placental ischemia/reperfusion-induced release of hypertensive substances into the maternal circulation. These include antiangiogenic and pro-inflammatory factors. There is also evidence implicating increased sympathetic nervous system activity (SNA) in this maternal disorder, but this mostly includes data correlating severity of disease with catecholamine levels and elevated muscle SNA. These measurements have not confirmed a causative role for SNA in the pathogenesis of preeclampsia. Therefore, studies are needed to provide a comprehensive understanding of SNA and its control of vascular function and blood pressure regulation during normal pregnancy in order to set the stage for exploring the mechanisms mediating the exaggerated SNA and signaling during preeclampsia. This review examines the role of SNA in control of uteroplacental vascular tone and blood pressure regulation during normal pregnancy. Furthermore, it is proposed that over-activation of the SNA contributes to altered uteroplacental vascular tone and perfusion leading to placental ischemic events and modulates the systemic vasoconstriction and hypertensive responses to soluble placenta ischemic factors. Recognizing the integrative role and importance of SNA in the pathophysiology of preeclampsia will advance our understanding of this maternal disorder.

The Effects of Controlled Tempo Manipulations on Cardiovascular Autonomic Function

Music has been associated with alterations in autonomic function. Tempo, the speed of music, is one of many musical parameters that may drive autonomic modulation. However, direct measures of sympathetic nervous system activity and control groups and/or control stimuli do not feature in prior work. This article therefore reports an investigation into the autonomic effects of increases and decreases in tempo. Fifty-eight healthy participants (age range: 22–80 years) were randomly allocated to either an experimental ( n = 29, tune) or control (rhythm of the same tune) group. All participants underwent five conditions: baseline, stable tempo (tune/rhythm repeatedly played at 120 bpm), tempo increase (tune/rhythm played at 60 bpm, 90 bpm, 120 bpm, 150 bpm, 180 bpm), tempo decrease (tune/rhythm played at 180 bpm, 150 bpm, 120 bpm, 90 bpm, 60 bpm) and recovery. Heart rate, blood pressure, respiration, and muscle sympathetic nerve activity were continuously recorded. The 60 bpm in the tempo decrease stimulus was associated with increases in measures of parasympathetic activity. The 180 bpm in the tempo increase stimulus was also associated with shifts towards parasympathetic predominance. Responses to the stimuli were predicted by baseline %LF. It is concluded that the individual tempi impacted upon autonomic function, despite the entire stimulus having little effect. The 60 bpm in an increasingly slower stimulus was associated with greater vagal modulations of heart rate than faster tempi. For the first time, this study shows that response direction and magnitude to tempo manipulations were predicted by resting values, suggesting that music responders may be autonomically distinct from non-responders.

Altered autonomic control of heart rate variability in the chronically hypoxic fetus.

Key points Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with fetal compromise. However, the mechanisms by which FHRV is reduced in the chronically hypoxic fetus have yet to be established.The sympathetic and parasympathetic influences on heart rate mature at different rates throughout fetal life, and can be assessed by time domain and power spectral analysis of FHRV.In this study of chronically instrumented fetal sheep in late gestation, we analysed FHRV daily over a 16 day period towards term, and compared changes between fetuses of control and chronically hypoxic pregnancy.We show that FHRV in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the sympathetic control of the fetal heart rate. This presents a potential mechanism by which a reduction in indices of FHRV predicts fetuses at increased risk of neonatal morbidity and mortality in humans.Reduction in overall FHRV may therefore provide a biomarker that autonomic dysregulation of fetal heart rate control has taken place in a fetus where uteroplacental dysfunction is suspected. Although fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced in the chronically hypoxic fetus have yet to be established. In particular, the physiological mechanism underlying the reduction of short term variation (STV) in fetal compromise remains unclear. In this study, we present a longitudinal study of the development of autonomic control of FHRV, assessed by indirect indices, time domain and power spectral analysis, in normoxic and chronically hypoxic, chronically catheterised, singleton fetal sheep over the last third of gestation. We used isobaric chambers able to maintain pregnant sheep for prolonged periods in hypoxic conditions (stable fetal femoral arterial PO2 10–12 mmHg), and a customised wireless data acquisition system to record beat‐to‐beat variation in the fetal heart rate. We determined in vivo longitudinal changes in overall FHRV and the sympathetic and parasympathetic contribution to FHRV in hypoxic (n = 6) and normoxic (n = 6) ovine fetuses with advancing gestational age. Normoxic fetuses show gestational age‐related increases in overall indices of FHRV, and in the sympathetic nervous system contribution to FHRV (P < 0.001). Conversely, gestational age‐related increases in overall FHRV were impaired by exposure to chronic hypoxia, and there was evidence of suppression of the sympathetic nervous system control of FHRV after 72 h of exposure to hypoxia (P < 0.001). This demonstrates that exposure to late gestation isolated chronic fetal hypoxia has the potential to alter the development of the autonomic nervous system control of FHRV in sheep. This presents a potential mechanism by which a reduction in indices of FHRV in human fetuses affected by uteroplacental dysfunction can predict fetuses at increased risk.

Effects of Sympathetic Activation on Aortic Stiffness in Young Healthy and Hypertensive Adults

Aortic stiffness is a major link between hypertension and cardiovascular risk. Anatomic features of the artery including the smooth muscle regulate aortic stiffness, in part. Importantly, vascular smooth muscle is under sympathetic nervous system control, and thus aortic stiffness may be influenced by the sympathetic nervous system. When exposed to physiological stress, older hypertensive adults demonstrate an exaggerated blood pressure response that may correspond with transient arterial stiffness increases, but this response in young hypertensive adults remains unknown.PURPOSEWe tested the hypothesis that sympathetic activation would increase aortic stiffness in young healthy adults (control, CTL), and that aortic stiffness increases during sympathetic activation would be greater in young hypertensive adults (HTN).METHODSSix healthy controls (males=4, females=2; 28.3±5.5 years; BMI: 23.5 ± 3.5 kg/m2) and three young hypertensive participants (males=2, females=1; 28.3±6.0 years; BMI: 30.3±8.2 kg/m2) were studied. Mean arterial pressure (MAP) and carotid‐femoral pulse wave velocity (PWV) were measured at rest and during 5 min of brachial circulatory occlusion (sympathetic activation condition) that followed isometric handgrip exercise.RESULTSResting MAP was higher in HTN (100±6 mmHg) than CTL (90±5 mmHg; P=.029). Occlusion MAP was also higher in HTN (116±6 mmHg) than CTL (102±7 mmHg; P=.016). Resting PWV was similar between CTL (8.6±1.6 m/s) and HTN (8.1±0.1 m/s; P=.47). The increase in PWV from rest to occlusion (1.2±1.4 m/s) in CTL was not significant (P=.09), whereas the increase in PWV from rest to occlusion (2.0±0.4 m/s) in HTN was significant (P=.01).CONCLUSIONSympathetic activation may significantly increase aortic stiffness in young hypertensive adults, but not young healthy adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

From white to beige: a new hypothalamic pathway.

Understanding how brown and beige adipocytes can be differentially controlled and activated by neuronal circuits is a fundamental prerequisite to fully comprehend the metabolic role that fat tissue plays in energy homeostasis. In this issue of EMBO reports, Wang et al [1] identify a new hypothalamic route that drives the exclusive recruitment of beige fat via the selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue. Since the data strongly suggest that the APPL2–AMPK signaling axis is crucial for this activation, this finding sheds a new light on the cross talk between peripheral homeostatic signals and neurons that are part of hypothalamic energy homeostasis regulatory pathways in the ventromedial hypothalamus (VHM) proposing a new defending mechanism to cold and obesity.

Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity.

Hypertension-Linked Pathophysiological Alterations in the Gut.

Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension. Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension. Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut-neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology. A dysfunctional sympathetic-gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.

Autonomic Nervous System Responses to Concussion: Arterial Pulse Contour Analysis.

The arterial pulse wave (APW) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system (SNS) control. With a transition from rest to increased metabolic demand, the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW. Following a sports concussion, a transient state cardiovascular autonomic dysfunction is present. How this state affects the APW has yet to be described. A prospective, parallel-group study on cardiovascular autonomic control (i.e., digital electrocardiogram and continuous beat-to-beat blood pressure) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes. Changes in APW were compared at rest and during the first 60 s (F60) of an isometric handgrip test (IHGT) in concussed athletes and non-injured controls within 48 h and 1 week of injury. The concussion group was further separated by the length of time until they were permitted to return to play (RTP > 1week; RTP ≤ 1week). SysSlope, an indirect measurement of stroke volume, was significantly lower in the concussion group at rest and during F60 at 48 h and 1week; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60. The RTP > 1week group had lower SysSlope (405 ± 200; 420 ± 88; 454 ± 236 mmHg/s, respectively) at rest 48 h compared to the RTP ≤ 1week and controls. Similarly at 48 h rest, several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls: peak-to-notch latency (0.12 ± 0.04; 0.16 ± 0.02; 0.17 ± 0.05, respectively), notch relative amplitude (0.70 ± 0.03; 0.71 ± 0.04; 0.66 ± 0.14, respectively), and stiffness index (6.4 ± 0.2; 5.7 ± 0.4; 5.8 ± 0.5, respectively). Use of APW revealed that concussed athletes have a transient increase in peripheral artery stiffness, which may be a compensatory adaptation to a paradoxical decline of stroke volume during the transition from rest to a state of increased metabolic demand within 48 h of concussion. This dysfunction of the SNS appeared to be more pronounced among concussed athletes who were removed from participation for >1 week compared to those who resumed play within 7 days.

Sympathetic Nervous System Control of Carbon Tetrachloride-Induced Oxidative Stress in Liver through α-Adrenergic Signaling.

In addition to being the primary organ involved in redox cycling, the liver is one of the most highly innervated tissues in mammals. The interaction between hepatocytes and sympathetic, parasympathetic, and peptidergic nerve fibers through a variety of neurotransmitters and signaling pathways is recognized as being important in the regulation of hepatocyte function, liver regeneration, and hepatic fibrosis. However, less is known regarding the role of the sympathetic nervous system (SNS) in modulating the hepatic response to oxidative stress. Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma. Mice treated with 6-hydroxydopamine hydrobromide were used to realize chemical sympathectomy. Carbon tetrachloride (CCl4) injection was used to induce oxidative liver injury. Sympathectomized animals were protected from CCl4 induced hepatic lipid peroxidation-mediated cytotoxicity and genotoxicity as assessed by 4-hydroxy-2-nonenal levels, morphological features of cell damage, and DNA oxidative damage. Furthermore, sympathectomy modulated hepatic inflammatory response induced by CCl4-mediated lipid peroxidation. CCl4 induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist. We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.

Hindlimb unweighting does not alter vasoconstrictor responsiveness and nitric oxide-mediated inhibition of sympathetic vasoconstriction.

Physical inactivity increases the risk of cardiovascular disease and may alter sympathetic nervous system control of vascular resistance. Hindlimb unweighting (HU), a rodent model of physical inactivity, has been shown to diminish sympathetic vasoconstrictor responsiveness and reduce NO synthase expression in isolated skeletal muscle blood vessels. Our understanding of the effects of HU on sympathetic vascular regulation in vivo is very limited. The present findings demonstrate that HU did not alter sympathetic vasoconstrictor responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. This study suggests that short-term physical inactivity does not alter in vivo sympathetic vascular control in the skeletal muscle vascular bed at rest and during contraction. We tested the hypothesis that physical inactivity would increase sympathetic vasoconstrictor responsiveness and diminish NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague-Dawley rats (n=33) were randomly assigned to sedentary time control (S) or hindlimb unweighted (HU) groups for 21days. Following the intervention, rats were anaesthetized and instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5Hz was determined at rest and during triceps surae muscle contraction before (control) and after NO synthase blockade with l-NAME (5mgkgi.v.). Sympathetic vasoconstrictor responsiveness was not different (P>0.05) in S and HU rats at rest (S, 2Hz, -26±8% and 5Hz, -46±12%; and HU, 2Hz, -29±9% and 5Hz, -51±10%) and during contraction (S, 2Hz, -10±7% and 5Hz, -23±11%; and HU, 2Hz, -9±5% and 5Hz, -22±7%). Nitric oxide synthase blockade caused a similar increase (P>0.05) in sympathetic vasoconstrictor responsiveness in HU and S rats at rest (S, 2Hz, -41±7% and 5Hz, -58±8%; and HU, 2Hz, -43±6% and 5Hz, -63±8%) and during muscle contraction (S, 2Hz, -15±6% and 5Hz, -31±11%; and HU, 2Hz, -12±5% and 5Hz, -29±8%). Skeletal muscle NO synthase expression and ACh-mediated vasodilatation were also not different between HU and S rats. These data suggest that HU does not alter sympathetic vasoconstrictor responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle.

The interplay between sympathetic overactivity, hypertension and heart rate variability (review, invited).

The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation.

Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies

Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a prominent role of the hypothalamus in TG metabolism through innervating the liver, WAT, and BAT mainly via sympathetic branches of the autonomic nervous system. Here, we review the recent findings in the area of sympathetic control of TG metabolism. Various neuronal populations, such as neuropeptide Y (NPY)-expressing neurons and melanocortin-expressing neurons, as well as peripherally produced hormones (i.e., GLP-1, leptin, and insulin), modulate sympathetic outflow from the hypothalamus toward target organs and thereby influence peripheral TG metabolism. We conclude that sympathetic stimulation in general increases lipolysis in WAT, enhances VLDL-TG production by the liver, and increases the activity of BAT with respect to lipolysis of TG, followed by combustion of fatty acids toward heat. Moreover, the increased knowledge about the involvement of the neuroendocrine system in TG metabolism presented in this review offers new therapeutic options to fight hypertriglyceridemia by specifically modulating sympathetic nervous system outflow toward liver, BAT, or WAT.

The Hemodynamic Actions of Insulin Are Blunted in the Sublesional Microvasculature of Healthy Persons with Spinal Cord Injury

The aim of this study was to gain a better understanding of the hemodynamic actions of insulin on cutaneous microcirculation in persons with spinal cord injury (SCI). A prospective, open-label, nonrandomized, placebo-controlled investigation was performed in an otherwise healthy cohort of persons with SCI (n = 10) and in an age- and sex-matched cohort of control subjects whose neurologic function is intact (n = 10). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) response (percent change from baseline) to insulin or placebo iontophoresis above and below the neurologic level of injury. Placebo iontophoresis did not result in any statistically significant changes in BPU. In the arm, insulin iontophoresis resulted in a 20% mean increase in BPU (P < 0.05) in the control group and a 9% mean increase in the SCI group (P = 0.14). In the leg, insulin iontophoresis resulted in an 81% (P < 0.01) mean increase in BPU in the control group and a 29% (P < 0.001) mean increase in BPU in the SCI group. The relative effect of insulin on the lower extremity BPU response was significantly greater (P < 0.05) in the control group compared with the SCI group (77% vs. 35%, respectively). The hemodynamic actions of insulin are markedly blunted in the sublesional microvasculature of persons with SCI, most likely as a result of impaired sublesional sympathetic nervous system control.

Leg vasoconstriction during head-up tilt in patients with autonomic failure is not abolished

Maintaining blood pressure during orthostatic challenges is primarily achieved by baroreceptor-mediated activation of the sympathetic nervous system, which can be divided into preganglionic and postganglionic parts. Despite their preganglionic autonomic failure, spinal cord-injured individuals demonstrate a preserved peripheral vasoconstriction during orthostatic challenges. Whether this also applies to patients with postganglionic autonomic failure is unknown. Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. Ten healthy subjects served as controls. Leg blood flow was measured using duplex ultrasound in the right superficial femoral artery. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. DBH-deficient patients were tested off and on the norepinephrine pro-drug l-threo-dihydroxyphenylserine (l-DOPS). During 60° head-up tilt, leg vascular resistance increased significantly in PAF patients [0.40 ± 0.38 (+30%) mmHg·ml(-1)·min(-1)]. The increase in leg vascular resistance was not significantly different from controls [0.88 ± 1.04 (+72%) mmHg·ml(-1)·min(-1)]. In DBH-deficient patients, leg vascular resistance increased by 0.49 ± 0.01 (+153%) and 1.52 ± 1.47 (+234%) mmHg·ml(-1)·min(-1) off and on l-DOPS, respectively. Despite the increase in leg vascular resistance, orthostatic hypotension was present in PAF and DBH-deficient patients. Our results demonstrate that leg vasoconstriction during orthostatic challenges in patients with PAF or DBH deficiency is not abolished. This indicates that the sympathetic nervous system is not the sole or pivotal mechanism inducing leg vasoconstriction during orthostatic challenges. Additional vasoconstrictor mechanisms may compensate for the loss in sympathetic nervous system control.

Editorial: Regulation of the regulator: sympathetic nervous system control of regulatory T cells

Abstract Discussion of data presented by Bhowmick et al. and the current knowledge of symptomatic nervous system interactions with immune function.

Status epilepticus produces chronic alterations in cardiac sympathovagal balance

Status epilepticus (SE) activates the autonomic nervous system, increasing sympathetic nervous system control of cardiac function during seizure activity. However, lasting effects of SE on autonomic regulation of the heart, which may contribute to mortality following seizure activity, are unknown. Therefore, autonomic control of cardiac function was assessed following SE. Using Sprague-Dawley rats after 1-2 weeks of recovery from lithium-pilocarpine-induced SE or control procedures, we tested overall sympathovagal control of the heart, the individual contributions of the sympathetic and parasympathetic components of the autonomic nervous system, and baroreflex sensitivity. SE induced a chronic shift in sympathovagal balance toward sympathetic dominance resulting from decreased parasympathetic activity. Baroreflex sensitivity to increased blood pressure was also decreased, likely resulting from diminished vagal activation. Chronic alterations in autonomic regulation of cardiac function, characterized by increased sympathetic dominance, occur following SE and likely contribute to subsequent increased cardiac risk and mortality.

HRV and BPV neural network model with wavelet based algorithm calibration

The heart rate and blood pressure power spectrum, especially the power of the low frequency (LF) and high frequency (HF) components, have been widely used in the last decades for quantification of both autonomic function and respiratory activity. Discrete Wavelet Transform (DWT) is an important tool in this field. The paper presents a LF and HF fast estimator that uses artificial neural networks and Daubechies DWT processing techniques. Radial Basis Function and Multilayer Perceptron neural networks were designed and implemented for fast assessment of cardiovascular autonomic nervous system control. The training values to design the networks were obtained after heart rate and blood pressure wavelets processing. The designed neural structures assure a faster evaluation tool of the sympathetic and parasympathetic autonomic nervous system control of the cardiovascular function.