Sympathetic Activity Research Articles

A single-center clinical trial evaluating topical propranolol for preventing stress-induced hair loss.

There is currently a lack of pathological research on the hair loss caused by stress, and there is no effective treatment available. It has been previously reported that stress can cause sympathetic nerve activation and release of norepinephrine, which binds to beta-2 adrenergic receptors and causes a series of chemical reactions. Propranolol, as a beta-2 adrenergic receptors blocker, competitively antagonizes the effects of norepinephrine. We initiated a single-center clinical trial with a self-controlled approach to assess the effectiveness of topical applied hydrochloride salt of propranolol solution in preventing stress-induced hair loss in humans. A total of 20 volunteers were enrolled. 14 out of 20 volunteers experienced a significant reduction in the number of hair loss (p < .05) after using hydrochloride salt of propranolol solution. No local adverse reactions were found. This study showed hydrochloride salt of propranolol solution may alleviate stress-induced alopecia to a certain extent, which provides clues for the development of pharmaceutical interventions for the treatment of stress-induced alopecia.

Ultrastructure and cardiac impulse propagation: scaling up from microscopic to macroscopic conduction.

The standard conception of cardiac conduction is based on the cable theory of nerve conduction, which treats cardiac tissue as a continuous syncytium described by the Hodgkin-Huxley equations. However, cardiac tissue is composed of discretized cells with microscopic and macroscopic heterogeneities and discontinuities, such as subcellular localizations of sodium channels and connexins. In addition to this, there are heterogeneities in the distribution of sympathetic and parasympathetic nerves, which powerfully regulate impulse propagation. In the continuous models, the ultrastructural details, i.e. the microscopic heterogeneities and discontinuities, are ignored by 'coarse graining' or 'smoothing'. However, these ultrastructural components may play crucial roles in cardiac conduction and arrhythmogenesis, particularly in disease states. We discuss the current progress of modelling the effects of ultrastructural components on electrical conduction, the issues and challenges faced by the cardiac modelling community, and how to scale up conduction properties at the subcellular (microscopic) scale to the tissue and whole-heart (macroscopic) scale in future modelling and experimental studies, i.e. how to link the ultrastructure at different scales to impulse conduction and arrhythmogenesis in the heart.

Postprandial hypoglycaemia after gastric bypass in type 2 diabetes: pathophysiological mechanisms and clinical implications.

Postprandial hypoglycaemia (PPHG) is a frequent late complication of Roux-en-Y gastric bypass (RYGB) in people without diabetes. We aimed to examine the pathogenetic mechanisms of PPHG and its clinical consequences in people with a history of type 2 diabetes. In this case-control study, 24 participants with type 2 diabetes treated with RYGB (14 women; median [IQR] age 53.5 [13.8] years, BMI 29.3 [6.3] kg/m2, HbA1c 36.0 [6.2] mmol/mol [5.4% (0.6%)]) underwent a dual-tracer, frequently sampled, 300 min, 75 g OGTT for the diagnosis of PPHG (glucose nadir <3.0 mmol/l, or <3.3 mmol/l with symptoms). Plasma glucose, glucose tracers, insulin, C-peptide, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol and NEFAs were measured. Mathematical models were implemented to estimate glucose metabolic fluxes and beta cell function. ECG recordings, cognitive testing and hypoglycaemia awareness assessments were repeated during the OGTT. Glycaemic levels and dietary habits were assessed under free-living conditions. PPHG occurred in 12 (50%) participants, mostly without symptoms, due to excessive tracer-derived glucose clearance (mean group difference ± SE in AUC0-180 min +261±72 ml min-1 kg-1 × min) driven by higher whole-body insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter depending on lower insulin clearance and enhanced beta cell function, regardless of incretin hormones. PPHG participants also had defective counterregulatory hormone responses to hypoglycaemia, preventing a physiological increase in endogenous glucose production and the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. PPHG was associated with more frequent and prolonged hypoglycaemia on 14 day continuous glucose monitoring and alterations in free-living dietary habits. Our results demonstrate that post-bypass PPHG occurs frequently in individuals with a history of type 2 diabetes, often without warning symptoms, and expose its complex pathogenetic mechanisms, revealing potential therapeutic targets.

Iwilfin (eflornithine) approved by the FDA as the first and only oral maintenance therapy for high-risk neuroblastoma in adult and pediatric patients: Narrative review.

Neural crest progenitor cells give rise to neuroblasts, the growing nerve cells of the sympathetic nervous system. These cells can undergo changes leading to neuroblastoma, a malignancy responsible for 15% of all pediatric cancer-related deaths. The molecular pathogenesis of this pediatric cancer involves complex genetic alterations, such as MYCN amplification, chromosomal abnormalities, and gene expression changes. Despite aggressive therapies, survival rates for children with high-risk neuroblastoma (HRNB) have not improved significantly compared to those with less severe forms of the disease. This highlights the challenge of managing HRNB and underscores the need for new, effective treatments. A comprehensive treatment regimen, including immunotherapy, radiation therapy, myeloablative chemotherapy, and surgical removal, has been employed to achieve remission in HRNB patients. While dinutuximab beta immunotherapy is an effective and widely used treatment, it has several potential side effects that must be carefully monitored. New drugs are being developed to reduce these side effects without compromising efficacy. One such drug is DL-alpha-difluoromethylornithine (DFMO), approved by the FDA under the brand name Iwilfin. Numerous clinical trials have shown that DFMO, when used as maintenance therapy, significantly improves event-free survival and overall survival in neuroblastoma patients. However, DFMO has adverse effects that require continuous monitoring. Further research is needed to minimize these side effects and improve its efficacy, particularly in addressing resistance caused by long-term use.

Sympathetic Nerves, Salivary Secretion, and the Parched Mouth of Fear: Unraveling Historical Perspectives on Persistent Contradiction in Physiology Textbooks.

We have observed two starkly contradictory notions regarding the sympathetic influence on the salivary outflow in discussions with our students. Most of them believe that sympathetic nerves decrease salivation and are antagonistic to parasympathetic nerves. Some students, however, show awareness of the cooperative stimulatory action of both types of autonomic fibers. We have found a similar dichotomy in the descriptions of the sympathetic effect on secretion of the main salivary glands and their inconsistent illustrations in Anatomy/Physiology textbooks. We have investigated the historical roots of this discrepancy. Ludwig discovered excitatory actions of both parasympathetic and sympathetic nerves on salivary flow by 1856. The next year, Czermak proposed the hypothesis of an inhibitory effect of sympathetic nerves, observing their interference with salivation induced by the chorda tympani (i.e., parasympathetic) stimulation. Bernard and Eckhard soon confirmed Ludwig's findings, but Czermak's notion persisted because sympathetically evoked salivation was unstable and potentially abatable by glandular vasoconstriction. The salivary secretory response to moderate sympathetic nerve electrostimulation was reaffirmed by Langley who also discovered salivation in response to adrenaline injection at the beginning of the 20th century. A few years later, Cannon, on a purely theoretical basis, attributed the sensation of dry mouth occasionally associated with fear to hyposalivation induced by elevated sympathetic discharge. Despite subsequent researchers' inability to find unequivocal evidence of salivary flow reduction by sympathetic activation, Cannon's assumption gained acceptance in some textbooks. Most Anatomy/Physiology textbook authors, however, recognized the excitatory action of sympathetic nerves on salivary glands established by Ludwig and Bernard.

Establishment of a HFpEF model using female Dahl salt-sensitive rats: a valuable tool for elucidating the pathophysiology of HFpEF in women.

The pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains unclear, and effective treatments are limited. HFpEF is more prevalent in females, indicating potential gender differences in its pathogenesis. However, no female HFpEF model animals have been established. Hypertension is a major contributor to HFpEF, and sympathetic activation is thought to play a role in both conditions. This study aimed to establish a female HFpEF model using hypertensive Dahl salt-sensitive rats and to assess the presence of sympathetic activation. Seven-week-old female Dahl salt-sensitive rats were fed an 8% high-salt diet (HS group, n = 6), while a low-salt diet group (LS group, n = 9) served as controls. The HS group exhibited increased systolic blood pressure and heart rate. Echocardiography revealed an increased left ventricular (LV) wall thickness, a decreased E/A ratio, and an increased E/e' ratio, all indicative of diastolic dysfunction without reduced LV ejection fraction. Additionally, the HS group showed elevated LV end-diastolic pressure, LV weight, and lung weight, along with histological cardiomyocyte hypertrophy and interstitial fibrosis. Gene expression markers for cardiac hypertrophy and fibrosis were also increased. Renal function was significantly impaired, and plasma norepinephrine levels were elevated, consistent with heightened pre-sympathetic neuronal activity in the brain. In conclusion, high salt loading from 7 weeks of age in female Dahl salt-sensitive rats induced hypertensive HFpEF phenotypes with LV hypertrophy and fibrosis, and sympathetic activation by 16 to 19 weeks of age. This model provides a valuable tool for studying HFpEF pathophysiology in women.

A brain-to-liver signal mediates the inhibition of liver regeneration under chronic stress in mice

As the ability of liver regeneration is pivotal for liver disease patients, it will be of high significance and importance to identify the missing piece of the jigsaw influencing the liver regeneration. Here, we report that chronic stress impairs the liver regeneration capacity after partial hepatectomy with increased mortality in male mice. Anatomical tracing and functional mapping identified a neural circuit from noradrenergic neurons in the locus coeruleus (LC) to serotonergic neurons in the rostral medullary raphe region (rMR), which critically contributes to the inhibition of liver regeneration under chronic stress. In addition, hepatic sympathetic nerves were shown to be critical for the inhibitory effects on liver regeneration by releasing norepinephrine (NE), which acts on adrenergic receptor β2 (ADRB2) to block the proinflammatory macrophage activation. Collectively, we reveal a “brain-to-liver” neural connection that mediates chronic stress-evoked deficits in liver regeneration, thus shedding important insights into hepatic disease therapy.

Mechanical circulatory support reduces renal sympathetic nerve activity in an ovine model of acute myocardial infarction.

The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms of improvement in kidney function are not clear. We tested the hypothesis that mechanical circulatory support would result in a decrease in directly recorded renal sympathetic nerve activity (RSNA) and mediate the improvement in renal blood flow (RBF) in a setting of acute myocardial infarction (AMI)-induced left ventricular systolic dysfunction. An anaesthetized ovine model was used to induce AMI (n = 8) using injections of microspheres into the left coronary artery in one group. The second group did not undergo embolization (n = 6). The effects of mechanical circulatory support using the Impella CP on directly recorded renal sympathetic nerve activity were examined in these two groups of animals. Injection of microspheres resulted in a drop in mean arterial pressure (MAP) of 21 ± 4mmHg compared to baseline values (p < 0.05; n = 8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA; from 16 ± 5 to 21 ± 5 spikes/s; p < 0.05; n = 7). Impella CP support significantly increased MAP by 13 ± 1.5mmHg at pump level 8 (p < 0.05) in the AMI group. Incremental pump support resulted in a significant decrease in RSNA (p < 0.05) in both groups. At pump level P8in the AMI group, RSNA was decreased by 21 ± 5.5% compared to pump level P0 when the pump was not on. Our data indicate that the improvement in kidney function following mechanical circulatory support may be mediated in part by renal sympathoinhibition.

Organ-specific sympathetic innervation defines visceral functions.

The autonomic nervous system orchestrates thefunctions of the brain and body through the sympathetic and parasympathetic pathways1. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac-superior mesenteric ganglia (CG-SMG). Of note, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG-SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations.

Analysis of the Prognostic Impact of Heart Rate Deceleration Capacity on Type 2 Diabetes Mellitus with Ventricular Premature Contractions

At present, one of the greatest life-threatening risks for patients with type 2 diabetes is cardiovascular complications. According to relevant research, approximately 70% to 80% of these patients die due to cardiovascular disease. Compared to non-diabetic individuals, diabetic patients face a two- to four-fold higher risk of developing cardiovascular and cerebrovascular diseases, with vascular complications resulting in an average life expectancy reduction of about 12 years. Increasing evidence indicates that cardiovascular-related indicators become abnormal as early as the initial stages of type 2 diabetes. During this period, the likelihood of adverse cardiovascular events rises, and cardiac autonomic dysfunction (CAD) begins, disrupting the balance between the parasympathetic and sympathetic nervous systems and thereby increasing cardiovascular disease risk. Cardiac autonomic dysfunction is one of many severe complications, and ventricular premature contractions are common arrhythmias in patients with type 2 diabetes, often seen as key indicators of declining cardiac function. Continuous heart rate deceleration, observed as deceleration runs (DRs) in Holter ECGs, manifests as a gradual prolongation of consecutive RR intervals, an indicator useful in assessing cardiac autonomic neuropathy. Persistent hyperglycemia or pre-diabetic states are associated with coronary artery disease (CAD), and strict blood glucose control helps slow the progression of microvascular complications. HRV monitoring is an effective method for evaluating early-stage cardiovascular autonomic neuropathy (CAN), providing a quantitative assessment of autonomic function and aiding in diagnosing other vascular complications.

High-fat diet during lactation, as opposed to during adolescence or gestation, programs cardiometabolic and autonomic dysfunctions in adult offspring

The Developmental Origins of Health and Disease (DOHaD) concept has been established for three decades. Many studies have shown that, besides pregnancy, other plastic phases (mainly preconception, lactation, and infancy–adolescence) are also sensitive to environmental changes, including nutritional conditions, that can program health or disease later in life. This study compared the susceptibility of the gestation, lactation and adolescence to a high-fat diet (HFD) intervention to program rats into autonomic nervous system imbalance and cardiometabolic dysfunction in adulthood. Four groups of rats were studied: offspring from mothers exposed to a HFD (35% fat) or a standard chow diet (4.5% fat) during gestation (GEST and CONT groups, respectively), offspring from mothers exposed to the HFD during lactation (LAC), and adolescent rats exposed to the HFD (ADOL). Mothers treated during pregnancy exhibited a higher body mass, but nursing mothers presented the highest food energy intake and higher adiposity. Compared to the other groups, the LAC rats showed increased body mass gain, food energy intake, body fat, glucose intolerance and blood pressure. LAC group also showed increased parasympathetic activity. In contrast, LAC sympathetic nerve activity decreased compared with the other groups. The ADOL group exhibited mostly similar responses but of a smaller magnitude. This suggests that the lactation phase is the most sensitive to HFD programming for cardiometabolic dysfunction in adulthood and that early overnutrition may affect neural connections by altering the autonomic nervous system balance.

Sympathetic hypoactivity leads to hypocontractility of the corpus cavernosum in sickle cell mice: a mechanism contributing to priapism.

Priapism, a prevalent complication in sickle cell disease (SCD) patients, manifests as prolonged and painful erections unrelated to sexual arousal. The detailed mechanisms contributing to this condition, especially regarding sympathetic function in the corpus cavernosum that maintains penile flaccidity, remain to be elucidated. In this study, it was hypothesized that the pathways of the sympathetic nervous system would be down-regulated, thereby contributing to the development of ischemic priapism in sickle cell disease. This study aimed to investigate the contractions induced by stimulation of sympathetic terminals and the expression of tyrosine hydroxylase in the corpora cavernosa of Berkeley SCD mice. C57BL/6 mice (wild-type, WT) and Berkeley SCD mice were used. A total of 22 mice were used in this study, with 11 allocated to the WT group and 11 to the SCD group. Mice corpus cavernosum was dissected free and mounted in 7-mL organ baths containing Krebs solution. Noradrenergic contractions were obtained using electrical-field stimulation (4-32 Hz) in corpus cavernosum strips from WT and SCD mice. Measurements of tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured by western blot. The neurogenic contractions were significantly lower (P < 0.05) in the SCD group compared to WT group at all tested frequencies. The protein expression of both total tyrosine hydroxylase and tyrosine hydroxylase phosphorylated at Ser-31 was significantly decreased by approximately 46.28% (P = 0.01) and 55.32% (P = 0.03) in cavernosal tissues from the SCD group compared to the control group, respectively. In conclusion, sympathetic hypoactivity characterized by the downregulation of tyrosine hydroxylase contributes to the hypocontractility of the corpus cavernosum in Berkeley SCD mice. This suggests an impairment in the mechanism responsible for maintaining penile flaccidity, potentially predisposing to erections without sexual stimulation, similar to those observed in ischemic priapism. Pharmacological treatments aiming to restore sympathetic tone in the penis might hold promise for addressing ischemic priapism in SCD.

ADRENAL EPINEPHRINE FACILITATES ERYTHROPOIETIN GENE ACTIVATION BY HYPOXIA THROUGH β2 ADRENERGIC RECEPTOR INTERACTION WITH Hif-2α

Hypobaric hypoxia (HH) occurring at high altitude activates the sympathetic nervous system (SNS) and increases circulating erythropoietin (Epo) levels. Epo stimulates red blood cell production (erythropoiesis), enhancing oxygen transport in arterial blood to counteract hypoxemia. Present study tested the hypothesis that SNS contributes to Epo activation by HH through epinephrine (Epi) release from the adrenal medullae. Adult male C57B6 mice were exposed to 18 hours of HH (0.4 atm), and renal Epo mRNA and plasma Epo levels were measured. HH increased Epo mRNA and plasma Epo levels, and SNS activation, as indicated by elevated plasma NE and Epi levels. In adrenalmedullectomized mice, HH-induced Epo response was reduced, correlating with decreased circulating NE and absence of Epi elevation. Epi, but not NE infusion, mimicked the effects of HH in room air breathing mice. Epo responses to HH were reduced with β-adrenergic receptor (AR) blockade using dl-propranolol and in β2 adrenergic receptor knockout mice. Mice with heterozygous Hif-2α deficiency ( Hif-2α+/-), but not Hif-1α+/-, showed attenuated the Epo gene activation and elevated plasma Epo levels in response to HH and Epi infusion. These results demonstrate that adrenal Epi facilitates the Epo gene activation by HH through interaction of β2 AR with HIF-2α.

Intradialytic Hypertension in Maintenance Hemodialysis.

To summarize the current evidence regarding epidemiology, clinical pathophysiology, and latest therapeutic approaches for the management of intradialytic hypertension (IDH). IDH is a rather common complication of dialysis, affecting 10-15% of the patient population and significantly increasing the cardiovascular risk. Its pathophysiology involves multiple mechanisms, including volume and sodium overload, sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) overactivity, endothelial dysfunction, and arterial stiffness. IDH management requires a combination of nonpharmacological and pharmacological interventions. The first mainly focus on volume control through dry weight optimization and modification of dialysate sodium, as studies show that strict volume control or low dialysate sodium can significantly reduce intradialytic and ambulatory blood pressure (BP). Pharmacological interventions have also been examined in research studies. Beta-blockers, particularly those with vasodilatory properties, can effectively target mechanisms such as SNS overactivity and endothelial dysfunction, and have shown some promising results reducing both intradialytic and ambulatory BP. Other drugs classes have also been explored as potential therapeutic options for IDH management, though further research is needed to clarify the efficacy of these interventions. A tailored approach addressing both the underlying pathophysiological mechanisms and individualized patient is warranted for improving BP control and cardiovascular outcomes in this high-risk population.

Salivary alpha-amylase: A marker of stress in gynecological residents during a shoulder dystocia simulation scenario.

Salivary alpha-amylase (sAA) has been recently proposed as biomarker of stress responsiveness within the sympathetic nervous system, preferable to cortisol, since limitations related to cortisol measurement (e.g. diurnal and seasonal rhythms, drugs interferences). Several factors, as age, collection device and analytical methods, also influence sAA levels and interpretation. This study aims to assess whether sAA could be useful to evaluate the stress response, also verifying some sources of variability. To identify any sources of sAA variability, saliva samples were collected from eight healthy subjects at five different times (8:00, 10:00, 12:00, 14:00 and 16:00) over five consecutive days using two different collection devices. Saliva was then collected from 35 obstetric residents before and after a simulated shoulder dystocia scenario, one of the most traumatic birth events in the professional life of gynecologists, to assess the stress levels. Samples were analysed throughout two different assays. Heart rate (HR) of residents was also measured before and after simulation scenario. Residents self-collected two saliva samples 10 min apart on a typical day. Overall, sAA levels increased significantly from morning to afternoon. Levels varied between subjects, but no differences were found between days or sampling devices. sAA activity levels in samples from 35 residents were significantly higher than those obtained before the scenario took place (about ten minutes later). These results were confirmed by two different assays. Moreover, a similar trend was observed when HR was considered. No differences were observed between samples collected 10 minutes apart on a typical day. Salivary alpha-amylase activity is a reliable, quick, and efficient marker for stress response, then its measurement will be of potential interest in the field of stress-related disorders. However, it is important to consider the timing of sample collection before introducing sAA in a clinical setting.

Regulation of cardiac function by the autonomic nervous system.

The autonomic nervous system is critical for regulating cardiovascular physiology. The neurocardiac axis encompasses multiple levels of control, including the motor circuits of the sympathetic and parasympathetic nervous systems, sensory neurons that contribute to cardiac reflexes, and the intrinsic cardiac nervous system that provides localized sensing and regulation of the heart. Disruption of these systems can lead to significant clinical conditions. Recent advances have enhanced our understanding of the autonomic control of the heart, detailing the specific neuronal populations involved and their physiologic roles. In this review, we discuss this research at each level of the neurocardiac axis. We conclude by discussing the clinical field of neurocardiology and attempts to translate this new understanding of neurocardiac physiology to the clinic. We highlight the contributions of autonomic dysfunction in prevalent cardiovascular diseases and assess the current status of novel neuroscience-based treatment approaches.

Unraveling the complex interplay between curved tunnels and drivers’ physiological responses: An HRV perspective

This study aims to unravel the complex interplay between curved tunnels and drivers’ physiological responses from an HRV (Heart Rate Variability) perspective.A group of 30 individuals with valid driver’s licenses was selected, and their HRV was monitored while driving through four curved tunnels in Yunnan Province, China. HRV indicators such as RMSSD (Root Mean Square of Successive Differences), SDNN (Standard Deviation of Normal-to-Normal Intervals), LF (Low Frequency), and LF/HF (ratio of Low Frequency to High Frequency) were analyzed. The independent variables included tunnel radius, turn direction, and zone characteristics. The results demonstrated that the radius, turning, and zone of the curved tunnel significantly influenced drivers’ HRV. Specifically, as the tunnel radius decreased, the mean RMSSD and SDNN of drivers decreased, while the mean LF and LF/HF increased. In left turns, drivers had lower RMSSD and SDNN values but higher LF and LF/HF ratios compared to right turns. Additionally, drivers showed the highest mean RMSSD and SDNN in the entrance zone of the tunnel, followed by the middle zone, and the lowest in the exit zone. Conversely, the exit zone had the highest mean LF and LF/HF, followed by the middle zone, and the entrance zone had the lowest. These results indicate that the characteristics of the curved tunnel have a substantial impact on drivers’ physiological responses. A smaller tunnel radius leads to increased stress and cognitive load, as reflected by the decreased HRV metrics and increased sympathetic activity. Turning maneuvers, particularly left turns, result in asymmetry in autonomic responses, with lower RMSSD and SDNN and higher LF and LF/HF during left turns. The variations in HRV across different zones within the tunnel suggest that environmental cues play a role in sympathetic activation, with the exit zone showing the highest sympathetic activity. These findings offer significant insights into the relationship between tunnel conditions and drivers’ physiological responses, emphasizing the importance of considering these factors in road safety and human factors engineering. By comprehending how tunnel characteristics affect drivers’ autonomic nervous system responses, we can formulate strategies to enhance driver well-being and safety.

Effects of different postures on the hemodynamics and cardiovascular autonomic control responses to exercise in postural orthostatic tachycardia syndrome.

To assess the effects of two different body positions on the cardiovascular autonomic profile during a single bout of exercise in patients with postural orthostatic tachycardia syndrome (POTS). Thirteen patients with POTS and thirteen healthy controls (C) participated in the study. ECG, respiration, beat-by-beat arterial pressure and O2 consumption (VO2) were continuously recorded while on a cycle ergometer in supine and upright positions, before and during exercise (6min, 50 Watts). Spectral analysis of RR intervals and systolic arterial pressure (SAP) variability provided indexes of cardiac sympathovagal interaction (LF/HF ratio), cardiac vagal modulation (HFRR, high-frequency component of RR variability, ~ 0.25Hz), sympathetic vasomotor control (LFSAP, low-frequency component of SAP variability, 0.1Hz) and baroreflex sensitivity (BRS, αLF). While supine, patients with POTS showed lower HFRR and αLF, greater heart rate (HR), LF/HF and LFSAP, compared with C, suggesting cardiovascular sympathetic over-activity and reduced BRS. While sitting upright, POTS showed greater HR and reduced HFRR and αLF compared with C. During supine exercise, SAP, HR, LF/HF increased and HFRR and αLF decreased similarly in POTS and C. In POTS, upright sitting exercise was associated with slightly higher , a greater increase in HR whereas LFSAP was lower than in C. Upright exercise was associated with excessive enhancement of HR and a blunted increase of the sympathetic vasomotor control in POTS. Conversely, supine exercise-induced hemodynamic and autonomic changes similar in POTS and C, thus making supine exercise potentially more suitable for physical rehabilitation in POTS.

Sympathetic nervous activity (SNA) is a key factor in insulin resistance

Sympathetic nervous activity (SNA) is a key factor in insulin resistance

Sympathetic nerve promotes renal fibrosis by activating M2 macrophages through β2-AR-Gsa

Sympathetic nervous system overactivation is directly related to renal fibrosis. This study focused on the role of and mechanism by which sympathetic signaling regulates macrophage activation, as well as the contribution to renal fibrosis. Renal denervation alleviated tubular necrosis, tubulointerstitial fibrosis, and macrophage accumulation induced by unilateral ureteral obstruction and ischemia-reperfusion injury. In vitro, norepinephrine (NE) promoted macrophage alternative (M2) polarization by activating β2-adrenergic receptor (β2-AR) and heterotrimeric G stimulatory protein α-subunit (Gsa). The effects of NE-induced macrophage M2 polarization were blocked by a β2-AR selective antagonist and Gsa siRNA. Importantly, ablation of Gsa in macrophages alleviated tubulointerstitial fibrosis, macrophage accumulation, and M2 polarization in the renal ischemia-reperfusion injury model. Sympathetic nervous system overactivation regulates M2 polarization in macrophages as an important neuroimmune mechanism of renal fibrosis. The β2-AR-Gsa signaling pathway was responsible for NE-induced macrophage M2 polarization, which may be a therapeutic target for renal fibrosis.