Sympathetic Nervous System Activity Research Articles

Abstract 4136181: Automated Personalized Modulation of the Sympathetic “fight-or-flight” Reflex In Vivo Using Implantable Microdevices for Enhancing Neurocardiac Function and Reducing Mortality Risk.

Background: The sympathetic nervous system (SNS) is a critical regulator of cardiovascular function. Whereas acute SNS activation elicits positive inotropy and confers survival advantage, persistent SNS hyperactivity is maladaptive and can lead to arrhythmias, cardiac arrest and heart failure. Hypothesis: Automated optogenetic modulation of the sympathetic stress response in vivo enhances neurocardiac function while avoiding sympathetic hyperactivity-mediated pathological effects. Methods: In normal guinea pigs, we virally transduced excitatory and/or inhibitory channelrhodopsins to the stellate ganglia (SG), the primary sympathetic input to the heart. We studied in situ effects of graded activation of SG opsins (e.g., phasic vs tonic) on cardiac function (e.g., ECG, heart rate) with and without perfusing agents (e.g., β-blockers, antioxidants). In vivo studies used novel implanted µLED devices for wireless body signal streaming (e.g., ECG) and neurophotonic SG opsin modulation closed-loop to dynamic analyses of physiological demand versus ECG-based cardiac risk prediction. Results: Compared to baseline heart rate (218±16 bpm), pulsed activation of inhibitory opsins reduced heart rate by ~25% (156±12; delta=67±14 bpm; p<0.0003; N=5). Pulsed activation of excitatory opsins increased heart rate by ~30% (285±28; delta=65±19 bpm; p<0.0002; N=5). Interestingly, prolonged (>20 min) tonic excitation of the SG caused desensitization, possibly as an intrinsic safety mechanism. Whereas graded SG excitation or inhibition at different LED intensities elicited prompt changes in heart rate, repeated activation of excitatory opsins led to quick desensitization. Our ongoing studies are aimed at understanding how and when SG modulation can enhance cardiac function, trigger intrinsic cardioprotective mechanisms, or cause pathological effects. Conclusion: Automated neurophotonic optogenetic excitation or inhibition of the SG is a robust personalized strategy for modulating cardiovascular function. The ability to rapidly and accurately modulate the sympathetic stress reflex in a graded manner can lead to more timely, effective, and appropriate physiological responses while avoiding undesired pathophysiological responses.

Does Parent–Child Separation in Childhood Influence Individuals’ Depressive Symptoms in Emerging Adulthood? The Roles of Sympathetic Nervous System Activity and Beliefs About Adversity

Childhood separation may have a long-term impact on individuals’ depressive symptoms when they enter emerging adulthood. However, the biological and cognitive protective factors that could buffer the negative effect of parent–child separation remain unclear. In this study, 215 young adults ( Mage = 18.46 years, SD = 0.69, 40% male) were selected as participants to examine the association between duration of parent–child separation in childhood and depressive symptoms and to investigate the moderating roles of sympathetic nervous system activity and beliefs about adversity in this relationship. Results revealed that duration of parent–child separation and beliefs about adversity were associated with young adults’ depressive symptoms. Sympathetic nervous system activity moderated the association between duration of parent–child separation and young adults’ depressive symptoms, and this moderation varied by beliefs about adversity and gender. These findings have significant implications for future research and development of interventions for young adults with parent–child separation experience.

Cardiovascular reactivity during conversations about discrimination is buffered by social support among U.S. Latines

Racial discrimination is conceptualized as an acute and chronic stressor. Like other acute stressors, lab-based studies demonstrate acute effects of discrimination-related stressors on stress-related cardiovascular outcomes, including total cardiac output, blood pressure, and indices of sympathetic and parasympathetic nervous system activity. Critically, it is important to understand how individual and social factors buffer the experience of race-related acute stress. The current study extends existing work by measuring cardiovascular indices of stress during conversations about racial/ethnic discrimination and examines the moderating role of social support. Latine/Hispanic participants (N = 97) talked about personal discrimination experiences with either a close other or a research assistant they had never previously met. Participants in both conditions exhibited cardiovascular reactivity indicative of stress during the conversation. Additionally, patterns of reactivity reflected a more adaptive stress response and recovery profile when participants talked about discriminatory experiences with a close other relative to a stranger (less parasympathetic withdrawal during the stressor and more parasympathetic rebound during recovery). These patterns are consistent with a stress buffering account of social support, which suggests social bonds and community-level support are critical to consider in interventions to mitigate the harms of experiencing discrimination and prevent chronic health disparities.

Olfactory stimulation with multiple odorants prevents stress-induced cognitive and psychological alterations

Abstract Acute and chronic stress markedly affects behavior by triggering sympathetic nervous system activation and several hypothalamus-pituitary-adrenal-dependent responses. Brain regions of the limbic system are responsible for the regulation of stress response, and different reports have demonstrated that their activity can be influenced by olfactory stimuli. Here we report that, in mice exposed to acute restraint stress, olfactory stimulation employing a combination of three odorants, i.e., vanillin, limonene and green odor (trans-2-hexenal and cis-3-hexenol) decreased anxiety behavior, assessed in the elevated plus maze, and halted recognition and spatial memory deficits, as appraised in two different object recognition tasks. Of note, when applied singularly, the same odorants were unable to block the detrimental effects of stress. We also found that the multiple odorants stimulation prevented the development of depressive symptoms assessed by the sucrose splash test and forced swim test in an experimental model of depression, i.e., mice exposed to a chronic unpredictable stress paradigm, and reduced interleukin 1β levels in the prefrontal cortex of depressed mice. Collectively, our data indicate that olfactory stimulation counteracts the detrimental effects of acute and chronic stress on mood regulation and cognitive functions, thus representing a potential tool for the treatment of stress-induced disorders.

The activation of cardiac sympathetic nervous system in the non-culprit lesion is a strong prognostic predictor in patients with acute myocardial infarction

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, it remains to be determined whether regional assessment of cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion of the cardiac MIBG SPECT imaging could have prognostic value in patients with AMI. Purpose The purpose of this study is to investigate the prognostic impact of regional CSNA in patients with AMI. Methods We prospectively enrolled 122 patients with AMI who visited our emergency department and underwent primary percutaneous coronary intervention. The late heart-to-mediastinum ratio (HMR) and washout rate (WR) was calculated to assess CSNA in the whole heart from planar images of in the cardiac MIBG imaging. The MIBG SPECT image parameters were calculated for each coronary artery, and the average WR in the culprit and non-culprit lesion were evaluated to assess the regional status of CSNA in patients with AMI. Abnormal WR in planar image was defined as 34% or more, as previously reported. The cut-off value of late HMR in planar image, WR in the culprit and non-culprit lesions were determined by ROC analysis. The primary endpoint was major adverse cardiac event (MACE) including all cause death, myocardial infarction, hospitalization for heart failure and target lesion revascularization. Results During a mean follow-up period of 3.1±1.8 years, 25 of 122 patients underwent MACE. The late HMR (p=0.004), WR in planar image (p=0.002), WR in the culprit lesion (p=0.023), and WR in the non-culprit lesion (p<0.001) were significantly associated with MACE at univariate Cox proportional hazard analysis. The increased WR in the non-culprit lesion (defined as 28.3% or more: AUC 0.697 [0.576-0.817]) was significantly independently associated with MACE (hazard ratio: 4.36 [1.45-13.11], p=0.009) even adjusted by late HMR, WR in planar image or WR in the culprit lesion, while decreased HMR, abnormal WR in planar image and increased WR in the culprit lesion showed no significant association with MACE in the multivariate model with WR in the non-culprit lesion. Kaplan-Meier analysis revealed that patients with increased WR in the non-culprit lesion had significantly higher risk for MACE than those without increased WR (45% vs 11% p<0.001). Conclusion(s) The activation of cardiac sympathetic nervous system in the non-culprit lesion is particularly associated with poor prognosis in patients with acute myocardial infarction.MACE risk by WR in non-culprit lesion

Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy

Abstract Introduction Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients. Purpose This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients. Methods Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90). Results After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR > median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p<0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B). Conclusion Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.

A Study on the Physiological Diversity of Hand Bathing under Different Conditions

Achieving the best outcomes and ensuring patients are as comfortable as possible are crucial goals for healthcare professionals. Hospital stress has been linked to worsening patient outcomes and so it is important to implement methods for keeping patients calm. Targeting the autonomic nervous system through hand bathing could provide answers. Associate Professor Hajime Nakano and his collaborators at the Faculty of Nursing, Josai International University, Japan, used precise tools to measure the heart rates of patients bathing their hands in waterbaths maintained at carefully controlled temperatures. The researchers used a probe to non-invasively measure brain activation and found that hand bathing decreased sympathetic nervous system activity, increased parasympathetic nervous system activity and produced feelings of relaxation. Nakano and the team conducted another study in which they activated the sympathetic nervous system in volunteers with mental arithmetic and found that hand bathing significantly suppressed the activation. This led them to posit that thermal stimulation has the potential to impact the stress responses in patients and their motivation in a bidirectional manner, which indicated significant possibilities for clinical applications. The researchers are keen to explore how altering the temperature of the hand bath can positively impact patients and an optimum temperature be selected. The team wants to ensure that interventions are tailored to the unique needs of patients and, as such, observed responses under different conditions and collected vast data that has enabled them to consider a research design that accommodated individual differences.

Can HRV Biofeedback Training Improve the Mental Resilience of Icelandic Police Officers?

High heart rate variability (HRV) is increasingly recognized as an indicator of a healthy regulatory system, reflecting the dynamic balance between sympathetic (SNS) and parasympathetic (PSNS) nervous system activity. According to the neurovisceral integration model, this balance is managed by the central autonomic network (CAN), comprised of specific brain regions involved in emotional, attentional, and autonomic regulation. HRV thus reflects the performance of the cognitive, affective, and autonomic regulation system. Numerous studies support the relationship between HRV and the CAN, including research on HRV biofeedback training (HRVBF). Studies on the effectiveness of HRVBF for professions such as police officers have shown improvements in self-regulation, decision-making, and performance. However, few studies have specifically explored HRVBF's influence on HRV metrics in police officers, highlighting a need for further research. This study addresses this gap by randomly assigning 27 Icelandic police officers to intervention or wait-list control groups. The intervention group underwent a five-week HRVBF program, including group and individual training sessions. Results showed significant increases in HRV metrics for the intervention group, indicating improved autonomic function and stress resilience. Mental resilience increased significantly as measured by subjective measures of attentional control, mindful awareness, and reduced fatigue. These findings support the efficacy of HRVBF in enhancing HRV and mental resilience for police officers, suggesting its applicability and potential for integration into existing training programs.

The sympathetic nervous system in heart failure with preserved ejection fraction.

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.

Modulating Sympathetic Nervous System with the use of SGLT2 Inhibitors: Where There is Smoke, There is Fire?

Heart failure (HF) has become even more prevalent in recent years, as a result of improved diagnostics and an increase in the risk factors predisposing to its pathology. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as one of the key pharmacotherapy options for both reduced and preserved ejection fraction, providing cardio- and renoprotection and improving mortality and cardiovascular (CV) outcomes. The pleiotropism of SGLT2i has led to multiple efforts to understand their distinct pathophysiological interactions with various pathways, including microcirculation, endothelial dysfunction, and inflammation. More recently, the role of SGLT2i on the sympathetic nervous system (SNS) is starting to be recognized, especially as observations of retained or reduced heart rate (HR) despite volume contraction have been noted by investigators in the large clinical trials testing the safety and efficacy of these agents. Both preclinical and clinical studies have been performed, with conflicting results. Interestingly, in both settings, whilst there are indications of SNS modulation by SGLT2i, other studies contradict such findings, without showing, however, worsening of the autonomic homeostasis. Given the importance of neuromodulation in HF, in both pharmacological and interventional therapies, in this review, we aim to describe the role of SNS in CV disease, focusing on HF, analyse preclinical and clinical data regarding the efficacy of SGLT2i in modulating autonomic dysfunction by examining various markers of SNS activation, as well as provide the most plausible theoretical backgrounds on the mechanism of benefit of SNS from the inhibition of SGLT2 receptors.

Sympathetic Innervation of Interscapular Brown Adipose Tissue Is Not a Predominant Mediator of Oxytocin-Induced Brown Adipose Tissue Thermogenesis in Female High Fat Diet-Fed Rats.

Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (TIBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of brown adipose tissue (BAT). We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of interscapular brown adipose tissue (IBAT) contributes to its ability to activate BAT and reduce body weight in female high HFD-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate TIBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated TIBAT similarly between sham rats and denervated rats (p = NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 μg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N = 7-8/group). Chronic 4V OT reduced body weight gain (sham: -18.0 ± 4.9 g; denervation: -15.9 ± 3.7 g) and adiposity (sham: -13.9 ± 3.7 g; denervation: -13.6 ± 2.4 g) relative to vehicle treatment (p < 0.05) and these effects were similar between groups (p = NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (p < 0.05) and 3 (p < 0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (p < 0.05 vs. vehicle). Together, these findings suggest that (1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and (2) the effects of OT to reduce weight gain and adiposity translate to other female mouse models of diet-induced obesity (DIO).

The impact of inflammatory and oxidative stress biomarkers on the sympathetic nervous system in severe coronary atherosclerosis.

The present study aimed at evaluating the association between sympathetic nervous system activation (SNS) and the severity of coronary artery disease (CAD). In addition, we tested the hypothesis that inflammation and oxidative stress influence the SNS activation. Adult patients with severe CAD scheduled for coronary artery bypass graft (CABG) surgery were enrolled. SYNTAX I score was calculated based on coronary angiography. Systemic activation of the SNS was estimated through circulating levels of norepinephrine (NE). Plasma levels of pro-inflammatory cytokines (IL 1β, IL 6 and HIF 1α) and oxidative stress molecules (SOD-1 and LOX-1) were obtained prior to surgery. Circulating NE levels were significantly correlated with the severity of CAD, as assessed by the SYNTAX I score (p 0.002; r 0.329). Elevated levels of circulating pro-inflammatory markers were significantly correlated with increased NE concentrations (for IL-1β: p < 0.001, r = 0.49; for IL-6 and NE: p = 0.003, r = 0.32; for HIF-1α and NE: p = 0.049, r = 0.21). Additionally, oxidative stress molecules were associated with circulating NE levels (for SOD-1 and NE: p = 0.016, r = 0.26; for LOX-1 and NE: p = 0.004, r = 0.31). In patients with CAD referred for CABG, SNS activation, indicated by plasma NE levels, was correlated with disease severity as assessed by the SYNTAX I score, as well as with markers of inflammation and oxidative stress. This suggests that inflammation, oxidative stress, and SNS activation form an interconnected network, with each component influencing the others. It might be of interest to develop a scoring system including inflammation and oxidative stress markers to identify patients that require a more aggressive approach to lower inflammation, oxidative stress and modulate the sympathetic nervous system. This could be of use especially in the setting of a scheduled intervention -such as CABG surgery.

RGS Proteins in Sympathetic Nervous System Regulation: Focus on Adrenal RGS4.

The sympathetic nervous system (SNS) consists largely of two different types of components: neurons that release the neurotransmitter norepinephrine (NE, noradrenaline) to modulate homeostasis of the innevrvated effector organ or tissue and adrenal chromaffin cells, which synthesize and secrete the hormone epinephrine (Epi, adrenaline) and some NE into the blood circulation to act at distant organs and tissues that are not directly innervated by the SNS. Like almost every physiological process in the human body, G protein-coupled receptors (GPCRs) tightly modulate both NE release from sympathetic neuronal terminals and catecholamine (CA) secretion from the adrenal medulla. Regulator of G protein Signaling (RGS) proteins, acting as guanosine triphosphatase (GTPase)-activating proteins (GAPs) for the Gα subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins), play a central role in silencing G protein signaling from a plethora of GPCRs. Certain RGS proteins and, in particular, RGS4, have been implicated in regulation of SNS activity and of adrenal chromaffin cell CA secretion. More specifically, recent studies have implicated RGS4 in regulation of NE release from cardiac sympathetic neurons by means of terminating free fatty acid receptor (FFAR)-3 calcium signaling and in regulation of NE and Epi secretion from the adrenal medulla by means of terminating cholinergic calcium signaling in adrenal chromaffin cells. Thus, in this review, we provide an overview of the current literature on the involvement of RGS proteins, with a particular focus on RGS4, in these two processes, i.e., NE release from sympathetic nerve terminals & CA secretion from adrenal chromaffin cells. We also highlight the therapeutic potential of RGS4 pharmacological manipulation for diseases characterized by sympathetic dysfunction or SNS hyperactivity, such as heart failure and hypertension.

Childhood Maltreatment and Electrodermal Reactivity to Stress Among Pregnant Women.

There are competing theoretical hypotheses regarding the consequences of early adversity, such as childhood maltreatment, for individuals' autonomic nervous system activity. Research examining potential implications of child maltreatment for sympathetic nervous system activity, specifically, is scarce. In this preregistered study, we examined whether childhood maltreatment history is associated with pregnant adults' sympathetic responses to different stressors. This population is particularly relevant, given potential intergenerational consequences of pregnant individuals' physiological responses to stress. Pregnant women's (N=162) electrodermal levels were recorded while completing the Trier Social Stress Test (TSST), which elicits social-evaluative threat, and while watching a video of an unfamiliar infant crying, which was intended to activate the attachment system. Pregnant women's retrospective reports of childhood maltreatment were negatively associated with their electrodermal reactivity to the TSST and to the video of the infant crying. Follow-up analyses indicated that these associations were specific to reported experiences of childhood abuse and not childhood neglect. Altogether, these findings indicate that self-reported childhood maltreatment experiences, and childhood abuse in particular, may result in blunted activity of the sympathetic nervous system in response to multiple types of stressors.

Polycystic Ovarian Syndrome: Exploring Hypertension and Cardiometabolic Implications.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, with significant implications for cardiometabolic health. This review focuses on the relationship between PCOS and hypertension (HTN), an area that remains underexplored despite growing evidence of its importance. PCOS is characterized by hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovarian morphology (PCOM), all of which contribute to a complex metabolic profile that includes insulin resistance (IR), obesity, and dyslipidemia. These factors collectively exacerbate the risk of HTN. Emerging research suggests HA in PCOS may directly influence the renin-angiotensin system (RAS), increasing blood pressure by promoting sodium retention and vascular tone. Additionally, IR, prevalent in both lean and obese women with PCOS, further contributes to HTN by enhancing sympathetic nervous system activity and impairing endothelial function. Despite these associations, the direct link between PCOS and HTN has not been definitively established, warranting further investigation. This review synthesizes current knowledge on the etiology of PCOS and its metabolic consequences, highlighting the need for targeted research to clarify the mechanisms linking PCOS with HTN. Understanding these pathways is crucial for improving the management of PCOS and reducing cardiovascular risks in affected women. By addressing these gaps, this review underscores the importance of considering HTN as a significant comorbidity in PCOS and calls for more comprehensive studies to guide clinical practice.

Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity.

The mechanisms underlying obesity-induced insulin resistance remain incompletely understood, as impaired cellular insulin signaling, traditionally considered the primary driver of insulin resistance, does not always accompany impaired insulin action. Overnutrition rapidly increases plasma norepinephrine (NE), suggesting overactivation of the sympathetic nervous system (SNS). However, the role of the SNS in obesity is controversial, as both increased and decreased SNS activity (SNA) have been reported. Here, we show that reducing catecholamine (CA) release from the SNS protects against overnutrition-induced insulin resistance as well as hyperglucagonemia, adipose tissue dysfunction, and fatty liver disease, as we demonstrate utilizing a mouse model of inducible and peripherally restricted deletion of tyrosine hydroxylase (th; THΔper). A key mechanism through which heightened SNA induces insulin resistance is by triggering adipose tissue lipolysis. Increased SNA emerges as a critical driver in the pathogenesis of overnutrition-induced insulin resistance and metabolic disease independent of cellular insulin signaling.

Is there an association between skeletal health and sympathetic nervous system activity in older adults?

Is there an association between skeletal health and sympathetic nervous system activity in older adults?

The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection

Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infections in the United States, known for triggering severe disease by hyperactivation of the host response. In this study, we determine the impact of the sympathetic nervous system (SNS) on CDI disease severity. Mouse models of CDI are administered inhibitors of SNS activity prior to CDI. Chemical sympathectomy or pharmacological inhibition of norepinephrine synthesis greatly reduces mortality and disease severity in the CDI model. Pharmacological blockade or genetic ablation of the alpha 2 adrenergic receptor ameliorates intestinal inflammation, disease severity, and mortality rate. These results underscore the role of the SNS and the alpha 2 adrenergic receptor in CDI pathogenesis and suggest that targeting neural systems could be a promising approach to therapy in severe disease.

Assessing the Sympatholytic Effects of SGLT2 Inhibitors in Anuric Haemodialysis Patients Using Microneurography: Study Protocol for a Mechanistic Proof-of-Concept Trial

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been shown to provide effective cardiorenal protection, reducing mortality in conditions such as heart failure and chronic kidney disease. While several mechanisms have been identified, recent research has shed light on the drug’s ability to attenuate sympathetic nervous system (SNS) activity. Controversy exists on whether this is due to the extra-renal effects of the drug, or simply due to its renoprotective effects. However, recent trials have highlighted the persistent efficacy of SGLT2i despite declining renal function. Therefore, investigating the ability of SGLT2i to attenuate the SNS independently of the kidney could lead to more insight into its mechanism of action. So far, there has been limited research done on investigating the extra-renal effects of SGLT2i in human subjects on dialysis where the glycosuric renal effects of SGLT2i are negligible. This current study therefore aims to investigate the effects of SGLT2i on the SNS in anuric haemodialysis patients. Methods: We developed a protocol for a mechanistic study to investigate the extra-renal effects of SGLT2i on the SNS. The study will be an investigator-led, open-label, prospective study involving 20 adult (aged ≥18 years) haemodialysis patients with a residual urine output of ≤250 mL/day. Participants will be administered empagliflozin 25 mg/day for 6 weeks. Baseline SNS activity will be measured before and after administration by microneurography to assess central SNS outflow. Secondary outcomes such as changes from baseline in SNS stressor response, heart rate variability, and endothelial function will also be examined. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive in anuric haemodialysis patients. Discussion: This will be the first study evaluating the effects of SGLT2i on the SNS in haemodialysis subjects. This study aims to enhance our understanding of the potential role of SGLT2i-induced SNS reduction in the setting of markedly reduced renal function. The study has received ethics approval from the Royal Perth Hospital Human Research Ethics Committee (RGS0000003840) (Australian New Zealand Clinical Trials Registry [ANZCTR] ID: ACTRN12623001237673).

Aspects of arterial hypertension in young adults with obesity

The global prevalence of hypertension and obesity continues to rise, affecting increasingly young people. Obesity causes hypertension through a variety of mechanisms, including sympathetic nervous system activation, renin angiotensin aldosterone system, fluid and electrolyte dysregulation, inflammation, and adipokine imbalance. In turn, arterial hypertension can exacerbate obesity by altering metabolic pathways and increasing appetite. The pathophysiological features of hypertension are different between young overweight women and men. We performed a non-systematic literature review to thoroughly investigate mechanisms of pathogenetic interaction and mutual aggravation of high blood pressure and body mass index. The literature was reviewed from 2004 to the present in Russian and English using the PubMed Central, ScienceDirect, Google Scholar platforms, as well as a search in the archives of the journals Circulation and Cardiovascular Therapy and Prevention using the keywords listed below.