Sympathetic Nervous System Activity Research Articles

Primary Role of the Kidney in Pathogenesis of Hypertension.

Previous transplantation studies and the concept of 'nephron underdosing' support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation.

Association of Depression With Myocardial Infarction With Non-obstructive Coronary Arteries: A Systematic Review.

This systematic review examined the association between depression and myocardial infarction with non-obstructive coronary arteries (MINOCA). A comprehensive literature search was conducted using electronic databases, resulting in the inclusion of six small case-control and cohort studies reported from Spain, Australia, China, and Pakistan. The studies included various study designs, such as cohort studies, case-control studies, and prospective cohort studies. The results of the systematic review indicate a significant association between depression and MINOCA. Several studies reported a higher prevalence of depression among MINOCA patients compared to those with obstructive coronary artery disease. Additionally, depression was found to be associated with worse outcomes in MINOCA patients, including increased cardiovascular events, all-cause mortality, and reduced quality of life. Some studies suggest that psychological factors, such as chronic stress, inflammation, and altered sympathetic nervous system activity, may play a role in the development and progression of MINOCA in individuals with depression. The findings highlight the importance of considering depression as a potential risk factor and prognostic marker in MINOCA patients. Early identification and management of depression in these individuals may improve outcomes and quality of life. A multi-center randomized controlled trial is needed to better understand the underlying mechanisms and to develop targeted interventions for individuals with depression and MINOCA.

Salivary alpha-amylase stress reactivity in advanced-aged marmosets (Callithrix jacchus): Impacts of cognitive function and oral health status.

Salivary alpha-amylase (sAA) is an enzyme found in saliva and is considered a noninvasive biomarker for sympathetic nervous system activity. While a wide range of sAA activity in response to stress has been reported in nonhuman primates, the effects of stress on sAA activity in common marmosets are still unknown. We tested the hypothesis that advanced age and cognitive function may have an impact on stress-related sAA reactivity in marmosets. Thirteen marmosets (nine males and five females) had saliva samples collected during a stressful condition (manual restraint stress) at two different time points, with a 60-min interval. On the next day, the animals underwent the object recognition test (ORT, a type of cognitive test), and then oral examinations. The animals were categorized into two age groups: old (10-13 years), and very old (15-22 years). Irrespective of age, sAA levels showed a significant difference between T1 (mean 2.07 ± 0.86 U/mL) and T2 samples (mean 1.03 ± 0.67 U/mL), with higher values observed at T1 (p < 0.001). The intra-assay coefficients of variation (CV) for low and high sAA concentrations were 10.79% and 8.17%, respectively, while the interassay CVs for low and high sAA concentrations were 6.39% and 4.38%, respectively. Oral health issues were common but did not significantly impact sAA levels. The ORT indicated that the animals could recognize an object placed in the cage 6 h after familiarization. In conclusion, all marmosets showed a higher sAA concentration in the first saliva sample as compared to the second saliva sample collected 1 h later, indicating adaptation to stress. No significant differences in sAA levels were observed between sexes, ORT performance, or oral health. Our results indicate that autonomic responsivity and cognitive (memory) functions were preserved even in very old marmosets.

Heart Rate Variability and Cognition: A Narrative Systematic Review of Longitudinal Studies.

Heart rate variability (HRV) is a reliable and convenient method to assess autonomic function. Cross-sectional studies have established a link between HRV and cognition. Longitudinal studies are an emerging area of research with important clinical implications in terms of the predictive value of HRV for future cognition and in terms of the potential causal relationship between HRV and cognition. However, they have not yet been the objective of a systematic review. Therefore, the aim of this systematic review was to investigate the association between HRV and cognition in longitudinal studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Embase, PsycINFO and PubMed databases were searched from the earliest available date to 26 June 2023. Studies were included if they involved adult human subjects and evaluated the longitudinal association between HRV and cognition. The risk of bias was assessed with the Newcastle-Ottawa Scale for Cohort Studies. The results were presented narratively. Of 14,359 records screened, 12 studies were included in this systematic review, with a total of 24,390 participants. Two thirds of the studies were published from 2020 onwards. All studies found a longitudinal relationship between HRV and cognition. There was a consistent association between higher parasympathetic nervous system (PNS) activity and better cognition, and some association between higher sympathetic nervous system activity and worse cognition. Also, higher PNS activity persistently predicted better executive functioning, while data on episodic memory and language were more scant and/or controversial. Our results support the role of HRV as a biomarker of future cognition and, potentially, as a therapeutic target to improve cognition. They will need confirmation by further, more comprehensive studies also including unequivocal non-HRV sympathetic measures and meta-analyses.

A Comparative Study of the Tolerance to Stress Response Under Spinal Anaesthesia in Diabetic Versus Non-Diabetic Patients

INTRODUCTION: Activation of sympathetic nervous system, increase of catabolic hormone release and pituitary gland suppression are responses to surgical stress. Neural blockade via epidural or spinal anesthesia, intravenous administration of high-dose of strong opioid analgesics, and infusion of anabolic hormones such as insulin are three main methods for balancing stress responses to surgery. However, there are conflicting reports about the extent of autonomic disturbances occurring after inducing spinal anesthesia in diabetic patients due to underlying autonomic neuropathy. METHODOLOGY: An observational cohort study was conducted in an operative room of a tertiary health care center involving 25 diabetic patients and 25 non-diabetic patients to evaluate the tolerance to stress. The diabetic patients undergone an exercise tolerance test to evaluate for postural hypotension which would indicate presence of autonomic neuropathy. Stress parameters such as heart rate, mean blood pressure, blood glucose level, and temperature were measured at regular intervals pre, peri- and post-operatively. RESULTS: Intraoperative heart rate, mean blood pressure, and blood glucose level were high in diabetic patients with autonomic neuropathy (p≤0.05). Temperature was higher in diabetic patients with autonomic neuropathy initially (p≤0.05) and had a higher fall peri-and post-operatively (T=15 minutes, T=20 minutes, and T=after surgery). A significant differences in the parameters of stress response were observed in diabetic patients with autonomic neuropathy. CONCLUSION: By understanding the correlation between stress-response in diabetic patients with autonomic neuropathy peri-operatively will help the anesthetist to provide customized services to every patient

Efficacy of oral alprazolam in the management of perioperative anxiety in dental implant surgeries: A randomized controlled study

ABSTRACT Objectives: Surgical anxiety has emerged as a major limitation of implant surgery impeding its emergence as a leading choice of rehabilitation. It also triggers a series of physiological, emotional, and cognitive responses which adversely affects treatment outcomes and postoperative management. Hence, this study was designed specifically to address anxiety in patients undergoing dental implant surgeries. Materials and Methods: This study included 54 partially edentulous patients requiring single-implant rehabilitation. The patients were randomly assigned to the test group (Alprazolam group) and control group (Placebo group). Twenty-seven patients (test group) received Alprazolam 0.5 mg as a preemptive anxiolytic and 27 patients (control group) received a multivitamin tablet as placebo 1 h before implant surgery. Heart rate, blood pressure and respiratory rate of patients were measured to access the activation of sympathetic nervous system. Results: Oral administration of Alprazolam 1 h before the procedure showed significant reduction in preoperative anxiety in patients undergoing surgical placement of dental implants. Conclusion: Anxiolytic effect of Alprazolam mediated by binding to the alpha 1 subunit of GABA A receptor enhances the inhibitory effect on the nervous system. Preoperative administration of alprazolam 0.5 mg h prior, conceivably be standardized for management of surgical anxiety.

Effect of wrist orthoses on upper limb function, activities of daily living, and stress response.

This study examined the effects on upper limb function, activities of daily living, and stress responses when wearing a wrist orthosis made of padded fiberglass or thermoplastic and provided essential information for selecting an orthosis. Thirty-one healthy adults performed two tests while not wearing a wrist orthosis, wearing a padded fiberglass wrist orthosis, and wearing a thermoplastic wrist orthosis. The Purdue Pegboard Test examined upper limb control. In the second test, the actions indicated by the Hand20 questionnaire were performed while wearing a wrist orthosis. An electrocardiogram was obtained before and after each test to identify any changes in sympathetic nervous system activity. The Purdue Pegboard Test scores were significantly higher when not wearing a wrist orthosis than when wearing wrist orthosis, and the Hand20 scores for all question were significantly lower. Thermoplastic wrist orthoses had fewer restrictions for upper limb function compared to padded fiberglass wrist orthoses, however activities of daily living were more limited. The low frequency/high frequency ratio and high frequency measures showed no significant differences. Pegboard test scores and the Hand 20 scores suggest that a wrist orthosis causes restriction of upper limb function.

Central Angiotensin II type 1 receptor deficiency alleviates renal fibrosis by reducing sympathetic nerve discharge in nephrotoxic folic acid-induced chronic kidney disease.

Fibrosis after nephrotoxic injury is common. Activation of the paraventricular nucleus (PVN) renin-angiotensin system (RAS) and sympathetic nervous system (SNS) are common mechanism of renal fibrosis. However, there have limited knowledge about which brain regions are most affected by Angiotensin II (Ang II) after nephrotoxic injury, what role does Angiotensin II type 1a receptors (AT1R) signaling play and how this affects the outcomes of the kidneys. In nephrotoxic folic acid-induced chronic kidney disease (FA-CKD) mouse models, we have integrated retrograde tracer techniques with studies on AT1afl/fl mice to pinpoint an excessively active central pathway that connects the paraventricular nucleus (PVN) to the rostral ventrolateral medulla (RVLM). This pathway plays a pivotal role in determining the kidney's fibrotic response following injury induced by folic acid. FA-CKD (vs sham) had increased in the kidney SNS activity and Ang II expression in the central PVN. The activation of Ang II in the PVN triggers the activation of the PVN-RVLM pathway, amplifies SNS output, thus facilitating fibrosis development in FA-CKD mouse. Blocking sympathetic traffic or deleting AT1a in the PVN alleviated renal fibrosis in FA-CKD mice. The FA-CKD mice have increased the expression of Ang II in PVN, thereby activating AT1a-positive PVN neurons project to the RVLM, where SNS activity is engaged to initiate fibrotic processes. The Ang II in PVN may contribute to the development of kidney fibrosis after nephrotoxic folic acid-induced kidney injury.

The Relationship Between Sodium Consumption Patterns, Stress Levels, and Physical Activity with Hypertension of Elderly Participants at UPTD Puskesmas Rantau Tijang, Pugung District, Tanggamus Regency in 2022

A person with hypertension has a rise in blood pressure above the healthy range of &lt;120/&lt;80. The amount of sodium that the body retains can impact blood prduction. Via the sympathetic nervous system's activation, which causes blood pressure to rise intermittently, stress causes hypertension. A sufficient amount of regular exercise significantly lowers blood pressure in hypertensive individuals. Elderly people frequently experience health issues. Many of these illnesses are non-communicable diseases like high blood pressure. The Province of Lampung has a 31,9% prevalence of hypertension. According to data on hypertension in the Tanggamus district, 120,276 persons have the condition. The research objective was to determine the correlation between sodium consumption patterns, stress levels, and physical activity with hypertension in prolanis participants at the Rantau Tijang Public Health Center, Tanggamus Regency in 2022. This study used quantitative research using a cross-sectional research design. The population in this study were 63 people using the total sampling technique. Bivariate analysis in this study uses the Gamma test. The results showed a significant correlation between the level of stress and physical activity and hypertension with a p-value of 0,001 and 0,003 and no significant correlation between sodium consumption and hypertension with a p-value of 0,746.

Association between resting heart rate and low natural killer cell activity: a cross-sectional study.

Resting heart rate (RHR), a simple physiological indicator, has been demonstrated to be associated with inflammation and even metabolic disorders. This study aimed to investigate whether RHR is associated with natural killer cell activity (NKA) in a large population of healthy adults using a novel assay to measure NKA. This cross-sectional study included 7,500 subjects in the final analysis. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level <500 pg/mL. Subjects were categorized into four groups according to RHR as follows: C1 (≤ 60 bpm), C2 (60-70 bpm), C3 (70-80 bpm), and C4 (≥ 80 bpm). Individuals with higher RHR exhibited poorer metabolic and inflammatory profiles, with the prevalence of low NKA being highest in the highest RHR category. Compared with C1 as reference, the fully adjusted odd ratios (ORs) [95% confidence intervals (CIs)] for low NKA were significantly higher in C3 (OR: 1.37, 95% CI: 1.08-1.75) and C4 (OR: 1.55, 95% CI: 1.20-2.00). In addition, RHR was shown to exert indirect effects on NKA upon consideration of the mediation effect of serum cortisol in path analysis. Our findings confirm a significant link between elevated RHR and low NKA, and suggest the usefulness of RHR, a simple indicator reflecting increased sympathetic nervous system activity and stress, in predicting reduced immune function.

Effects of Renal Denervation on Ouabain‐Induced Hypertension in Rats

Background. Ouabain, a Na+, K+‐ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain‐induced hypertension. Methods and Results. Forty Sprague‐Dawley rats were divided into following groups (n = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure (P &lt; 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels (P &lt; 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN. Conclusions. The present study reveals that renal nerves play an important role in the development of ouabain‐induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels.

Lowering Effect of Potassium on Hypertension

Hypertension is the blood pressure (BP) that is higher than the normal values in the arteries. Dietary changes and other lifestyle adjustments are essential to its management. Potassium has become known as a crucial Mineral with potential blood pressure-lowering effects among the many dietary variables. The objective of this writing is to summarize the most recent research on the connection between potassium intake and hypertension. Multiple investigations have revealed an inverse association between blood pressure and potassium intake. In addition to increasing vasodilation, lowering sodium reabsorption, and improving renal function, potassium also has antihypertensive effects. Additionally, studies have demonstrated that eating diets high in potassium increase endothelial function, lessen arterial stiffness, and lessen sympathetic nervous system activity. According to current research, increasing potassium intake, primarily from dietary sources such as fruits, vegetables, and legumes, is an effective way for managing hypertension. Individual differences, potential drug interactions, and the need for additional research to determine the best consumption levels should all be taken into account. Overall, incorporation of potassium-rich foods in the diet shows promise as a natural strategy to lower blood pressure and mitigate the symptoms of hypertension.

Disruption of Atrial Rhythmicity by the Air Pollutant 1,2-Naphthoquinone: Role of Beta-Adrenergic and Sensory Receptors.

The combustion of fossil fuels contributes to air pollution (AP), which was linked to about 8.79 million global deaths in 2018, mainly due to respiratory and cardiovascular-related effects. Among these, particulate air pollution (PM2.5) stands out as a major risk factor for heart health, especially during vulnerable phases. Our prior study showed that premature exposure to 1,2-naphthoquinone (1,2-NQ), a chemical found in diesel exhaust particles (DEP), exacerbated asthma in adulthood. Moreover, increased concentration of 1,2-NQ contributed to airway inflammation triggered by PM2.5, employing neurogenic pathways related to the up-regulation of transient receptor potential vanilloid 1 (TRPV1). However, the potential impact of early-life exposure to 1,2-naphthoquinone (1,2-NQ) on atrial fibrillation (AF) has not yet been investigated. This study aims to investigate how inhaling 1,2-NQ in early life affects the autonomic adrenergic system and the role played by TRPV1 in these heart disturbances. C57Bl/6 neonate male mice were exposed to 1,2-NQ (100 nM) or its vehicle at 6, 8, and 10 days of life. Early exposure to 1,2-NQ impairs adrenergic responses in the right atria without markedly affecting cholinergic responses. ECG analysis revealed altered rhythmicity in young mice, suggesting increased sympathetic nervous system activity. Furthermore, 1,2-NQ affected β1-adrenergic receptor agonist-mediated positive chronotropism, which was prevented by metoprolol, a β1 receptor blocker. Capsazepine, a TRPV1 blocker but not a TRPC5 blocker, reversed 1,2-NQ-induced cardiac changes. In conclusion, neonate mice exposure to AP 1,2-NQ results in an elevated risk of developing cardiac adrenergic dysfunction, potentially leading to atrial arrhythmia at a young age.

YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy.

Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy (n = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to YB-1, whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of YB-1 in CMs, caused by infection with an adenovirus encoding YB-1 (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; n = 10-16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. YB-1 overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 (RGS2) under PE stimulation (n = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches.

Unveiling Catecholamine Dynamics in Cardiac Health and Disease: Mechanisms, Implications, and Future Perspectives

Review Unveiling Catecholamine Dynamics in Cardiac Health and Disease: Mechanisms, Implications, and Future Perspectives Wenjing Xiang, Xingyun Wang, Lei Li, Junhui Zeng, Haocheng Lu, and Ying Wang * Department of Pharmacology, School of Medicine, Southern University of Science and TechnologyShenzhen518055China * Correspondence: wangy6@sustech.edu.cn Received: 15 August 2023 Accepted: 21 September 2023 Published: 27 December 2023 Abstract: Catecholamines play a pivotal role in regulating both cardiac physiology and pathology, orchestrating the “Fight-or-flight” response through the activation of sympathetic nervous system (SNS) activation and subsequent stimulation of adrenergic receptor. However, chronic stress and various cardiac diseases can disrupt catecholamine balance, contributing to cardiac dysfunction. The synthesis, release, reuptake, and degradation of catecholamines intricately regulate their concentration. Notably, catecholamine dynamics is markedly altered in heart diseases, including heart failure, myocardial infarction, and arrhythmias. While β‍-adrenergic receptor blockers, which block catecholamines from binding to the adrenergic receptors, are widely used in clinical settings, the potential implication of directly manipulating catecholamine homeostasis for the treatment of cardiac diseases have not been extensively explored. This review provides an overview of catecholaminergic systems, and discusses their intricate synthesis, release, uptake, and metabolism within the heart. Additionally, the review highlights mechanisms underlying cardiac effects of catecholamine dysregulation, including contractile dysfunction, electrical remodeling, and cardiac remodeling. Moreover, the review emphasizes the importance of considering spatiotemporal and sexual heterogeneity in catecholamine dynamics for cardiac precision medicine. In terms of future perspectives, we believe that harnessing genetically encoded fluorescent biosensors to map the heterogenous for real-time imaging of catecholamine dynamics and conducting gender-specific dissection of catecholamine dynamics have significant potential to advance personalized management of cardiac diseases management.

Autonomic nervous system function before and after trauma-focused psychotherapy in youth with (partial) posttraumatic stress disorder

While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous system (ANS) associated with PTSD, remains incompletely understood. During neutral and personalized trauma script imagery heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) were recorded in youth aged 8–18 with PTSD or partial PTSD (n = 76) and trauma-exposed controls (TEC) (n = 27) to determine ANS activity and stress reactivity. Within the patient group, 77.6% met the full DSM-IV diagnostic criteria for PTSD, the remaining 22.4% met the criteria for partial PTSD. Youth with (partial) PTSD were subsequently treated with eight sessions of either trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing. PTSD severity was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide patients into responders and non-responders. Youth with (partial) PTSD relative to TEC had higher overall HR during both neutral and trauma imagery (p = .05). Youth with (partial) PTSD showed RSA decrease during trauma imagery relative to neutral imagery, the reverse of TEC (p = .01). Relative to non-responders, responders demonstrated a significant baseline to posttreatment increase of RSA response to stress only when employing a ≥ 50% response criterion (p = .05) and not with the primary ≥ 30% criterion (p = .12). Our results suggest overall higher HR and sympathetic nervous system activity as well as vagal withdrawal in response to stress in youth with (partial) PTSD and only provide partial support for normalization of the latter with successful trauma-focused psychotherapy.

Ventromedial hypothalamus relays chronic stress inputs and exerts bidirectional regulation on anxiety state and related sympathetic activity.

Chronic stress can induce negative emotion states, including anxiety and depression, leading to sympathetic overactivation and disturbed physiological homeostasis in peripheral tissues. While anxiety-related neural circuitry integrates chronic stress information and modulates sympathetic nervous system (SNS) activity, the critical nodes linking anxiety and sympathetic activity still need to be clarified. In our previous study, we demonstrated that the ventromedial hypothalamus (VMH) is involved in integrating chronic stress inputs and exerting influence on sympathetic activity. However, the underlying synaptic and electrophysiological mechanisms remain elusive. In this study, we combined in vitro electrophysiological recordings, behavioral tests, optogenetic manipulations, and SNS activity analyses to explore the role of VMH in linking anxiety emotion and peripheral SNS activity. Results showed that the VMH played an important role in bidirectionally regulating anxiety-like behavior and peripheral sympathetic excitation. Chronic stress enhanced excitatory inputs into VMH neurons by strengthening the connection with the paraventricular hypothalamus (PVN), hence promoting anxiety and sympathetic tone outflow, an important factor contributing to the development of metabolic imbalance in peripheral tissues and cardiovascular diseases.

Fluid homeostatic action of dapagliflozin in patients with chronic kidney disease: the DAPA-BODY Trial.

Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group (n = 73) and a control group (n = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (-0.65% ± 2.03% vs. 0.97% ± 2.49%, p = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (-1.47% ± 1.93% vs. -0.01% ± 1.88%, p = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, p = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, p = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds. Clinical trial registration: https://www.umin.ac.jp/ctr/, identifier [UMIN000048568].

Analysis of QRS complex morphology in children and adolescents with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) leads to many cardiovascular, neurologic, metabolic, and neurocognitive consequences. Conduction deficits, deviations in electrical axis, and changes in QRS morphology reflect the impairments in cardiac muscle activity and underlie the cardiovascular complications of OSAS. Here we aimed to determine the relationship between OSAS and changes in the cardiac conduction system in children and adolescents. During the 6-month duration of the study, all children having the diagnosis of OSAS in Sleep and Disorders Unit following a full-night polysomnography (PSG) were consecutively evaluated. ECGs were performed and analyzed in the Division of Pediatric Cardiology, Department of Pediatrics. The maximum spatial vector size (QRSmax), QRS electrical axis (EA), left and right ventricular hypertrophy, and the presence of fragmented QRS (fQRS) or prolonged R or S wave were examined in detail. A total of 17 boys with OSAS and 13 healthy boys participated in the study. The mean QRSmax and the QRSmax on V5 derivative were significantly lower in the patient group compared to those in the control group (p = 0.011 and p = 0.017, respectively). EA was similar between the two groups. While none of the patients with OSAS nor the control group had left ventricular hypertrophy, only one boy with OSAS had right ventricular hypertrophy according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was significantly higher in patients with OSAS compared to healthy controls (p = 0.035), especially in children below the age of 5years (p = 0.036). Conclusion: This study demonstrated that male children and adolescents with OSAS have a combination of QRS complex changes characterized by low QRS voltages, and increased frequency of fragmented QRS. These findings reflect that the electrical remodeling and structural remodeling of the myocardium are considerably affected by OSAS in children and adolescents, leading to ventricular changes and intraventricular conduction problems. What is Known: • Pediatric obstructive sleep apnea syndrome (OSAS) characterized by recurrent intermittent hypoxemia, hypercapnia, and sleep fragmentation results in sympathetic nervous system activation, increased inflammation, and hypoxic endothelial dysfunction. When left untreated, OSAS leads to many cardiovascular, neurologic, metabolic and neurocognitive consequences, and also to sudden infant death syndrome in young children, probably due to the involvement of the cardiac conduction system. What is New: • This study demonstrated that mean QRSmax was significantly lower in male children and adolescents with OSAS, reflecting the structural and electrical remodeling of the myocardium, and one boy with OSAS had RVH according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was much higher in boys with OSAS, especially in children below the age of five years. These finding showed that myocardium was considerably affected to impair the intraventricular conduction in younger children with OSAS.

Hypertension in periand postmenopausal women: mechanisms, management, observation

An important role in the development and evolution of hypertension in females is applied to sex hormones. Estrogen deficiency and hyperandrogenism, characteristic of periand postmenopause, are links in the pathogenesis of hypertension in this period of a woman's life and are accompanied by an increase in sympathetic nervous system activity, renin-angiotensin-aldosterone system activation, salt sensitivity, abdominal obesity and metabolic syndrome, left ventricle hypertrophy, left atrial dilatation with a high risk of atrial fibrillation, stroke and heart failure development. The paper discusses antihypertensive therapy during periand postmenopause, effectiveness and tolerability of different drug classes. Special attention is paid to the mechanism of action of selective I1-imidazoline receptor agonist moxonidine, which in women during this period both effectively reduces high blood pressure and has a beneficial metabolic effect, what is documents in studies of monotherapy, combined antihypertensive therapy with major classes and in combination with menopausal hormone therapy. The paper presents the joint expert opinion concerning above mentioned issues.