Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.

Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

PharmaMemory: an interactive, animated web application for learning autonomic physiology and pharmacology.

Medical students face challenging but important topics they must learn in short periods of time, such as autonomic pharmacology. Autonomic pharmacology is difficult in that it requires students to synthesize detailed anatomy, physiology, clinical reasoning, and pharmacology. The subject poses a challenge to learn as it is often introduced early in medical school curricula. To ease the difficulty of learning autonomic pharmacology, we created a free web application, PharmaMemory (www.pharmamemory.com), that interactively depicts the effects of high-yield autonomic drugs on the human body. PharmaMemory provides users with the opportunity to read and quiz themselves on the mechanisms, side effects, indications, and contraindications of these drugs while interacting with the application. We provided PharmaMemory to first-year medical students for three consecutive years of quality improvement and assessed the application's perceived effects on learning via user surveys. Survey feedback showed that users viewed PharmaMemory favorably and self-reported increased knowledge and confidence in the subject of autonomic pharmacology. Comments revealed that users liked the website's visuals, opportunity for challenged recall, and conciseness. PharmaMemory utilizes challenged recall, visual stimulation, and interactive learning to provide users with a multifaceted learning tool. Preliminary data suggest that students find this method of learning beneficial. Further studies are needed to assess PharmaMemory compared with more traditional learning methods such as PowerPoint or text-based learning. Additionally, further research is needed to quantitatively assess reduction in cognitive load.NEW & NOTEWORTHY PharmaMemory (www.pharmamemory.com) is a free web application that interactively depicts the effects of high-yield autonomic drugs on the human body.

High-dose Chemotherapy Impairs Cardiac Autonomic Control of Hospitalized Cancer Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) patients have intermediary and late cardiac autonomic dysfunction, which is an independent mortality predictor. However, it is unknown when this HSCT-related autonomic dysfunction begins during hospitalization for HSCT and whether cardiac autonomic control (CAC) is related to cardiotoxicity in these patients. PATIENTS AND METHODS: CAC was assessed in 36 autologous-HSCT inpatients (HSCT group) and 23 cancer-free outpatients (CON group) using heart rate variability analysis. The HSCT group was assessed at five time-points from admission to hospital discharge during hospitalization period. The CON group was assessed once. The severity of cardiotoxicity (CTCAE 5.0) and cardiac troponin I were recorded. RESULTS: The CAC was significantly reduced after high-dose chemotherapy (HDC) (reduction of MNN, SDNN, RMSSD, LFms2 and HFnu, and increase of LFnu and LF/HF; P<0.05). At the onset of neutropenia, pNN50 and HFms2 were also reduced (P<0.05) compared to the admission ones. Although both groups were similar regarding CAC at hospital admission, the HSCT patients showed impaired CAC at hospital discharge (P<0.05). The LF/HF was positively associated with cardiac troponin I and RMSSD was inversely associated with the severity of cardiotoxicity (P≤0.05). CONCLUSION: CAC worsened during hospitalization for autologous-HSCT, mainly after HDC. In addition, it seems associated to early signs of cardiotoxicity in these patients.

Susceptibility of patients with chronic obstructive pulmonary disease to heart rate difference associated with the short-term exposure to metals in ambient fine particles: A panel study in Beijing, China.

Susceptibility of patients with chronic obstructive pulmonary disease (COPD) to cardiovascular autonomic dysfunction associated with exposure to metals in ambient fine particles (PM2.5, particulate matter with aerodynamic diameter ≤2.5 µm) remains poorly evidenced. Based on the COPDB (COPD in Beijing) panel study, we aimed to compare the associations of heart rate (HR, an indicator of cardiovascular autonomic function) and exposure to metals in PM2.5 between 53 patients with COPD and 82 healthy controls by using linear mixed-effects models. In all participants, the HR levels were significantly associated with interquartile range increases in the average concentrations of Cr, Zn, and Pb, but the strength of the associations differed by exposure time (from 1.4% for an average 9 days (d) Cr exposure to 3.5% for an average 9 d Zn exposure). HR was positively associated with the average concentrations of PM2.5 and certain metals only in patients with COPD. Associations between HR and exposure to PM2.5, K, Cr, Mn, Ni, Cu, Zn, As, and Se in patients with COPD significantly differed from those in health controls. Furthermore, association between HR and Cr exposure was robust in COPD patients. In conclusion, our findings indicate that COPD could exacerbate difference in HR following exposure to metals in PM2.5.

Production of Lactobacillus brevis ProGA28 attenuates stress-related sleep disturbance and modulates the autonomic nervous system and the motor response in anxiety/depression behavioral tests in Wistar-Kyoto rats.

AIMS: Many studies have reported that the production of Lactobacillus brevis is beneficial for sleep, but the underlying mechanism remains unclear. Other known beneficial effects of Lactobacillus brevis include improvement of anxious or depressive symptoms and better modulation of the autonomic nervous system, both of which impact sleep. In this study, we investigated whether the sleep benefit of Lactobacillus brevis was associated with the modulating effects on the autonomic nervous system and anxious/depressive symptoms. MAIN METHODS: Wistar-Kyoto rats were fed the production of Lactobacillus brevis (ProGA28) for the last 2 weeks of treatment before being exposed to case exchange (stress-induced insomnia paradigm). Waking, quiet sleep, and paradoxical sleep states were defined based on polysomnographic measurements. Autonomic functioning was assessed by heart rate variability (HRV). A combined behavioral test was used to evaluate anxiety-like or depressive-like behaviors after the following 2 days. KEY FINDINGS: In exposure to the dirty cage, the control group had significant prolongation of sleep latency, sleep loss during the first 2 h, and decreased parasympathetic activity and increased sympathetic activity during quiet sleep, which were significantly mitigated in the ProGA28 group. In behavioral tests, the ProGA28 group exhibited significantly less anxiety/depression-like motor responses in the elevated plus maze test, the forced swimming test, and the three-chamber social interaction test. Less initial sleep loss in the ProGA28 group was related to higher parasympathetic activity during quiet sleep, and shorter sleep latency in both groups was associated with longer time staying in the open arm in the elevated plus maze test. SIGNIFICANCE: These findings suggest that L. brevis ProGA28 can attenuate stress-related sleep disturbance, which may be associated with increased parasympathetic activity and decreased anxiety-like behaviors.

Competitive dynamics underlie cognitive improvements during sleep.

We provide evidence that human sleep is a competitive arena in which cognitive domains vie for limited resources. Using pharmacology and effective connectivity analysis, we demonstrate that long-term memory and working memory are served by distinct offline neural mechanisms that are mutually antagonistic. Specifically, we administered zolpidem to increase central sigma activity and demonstrated targeted suppression of autonomic vagal activity. With effective connectivity, we determined the central activity has greater causal influence over autonomic activity, and the magnitude of this influence during sleep produced a behavioral trade-off between offline long-term and working memory processing. These findings suggest a sleep switch mechanism that toggles between central sigma-dependent long-term memory and autonomic vagal-dependent working memory processing.

Impact of autoantibodies against the M2-muscarinic acetylcholine receptor on clinical outcomes in peripartum cardiomyopathy patients with standard treatment.

OBJECTIVES: To evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM). METHODS: A total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (-) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups. RESULTS: A total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (-) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (-) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (-) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (-) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (-) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (-) group, but all-cause mortality and cardiovascular mortality were the same. CONCLUSIONS: There were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (-) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R.

Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats.

Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Arterial BP, electrocardiographic, and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-wk-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using ultra-high performance liquid chromatography tandem mass spectrometry. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on cultured cardiomyocytes. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted predilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS.

There has been increasing emphasis on the importance of the development of self-regulatory capacities of the individual as the cornerstone of development. The caregivers' abilities to manage their own attention, emotions, physiology and behaviors influence the development of the child's self-regulatory and interactive capacities, and thereby their overall development. Newborns prenatally exposed to psychoactive substances and/or to other prenatal stressors such as maternal poor nutrition, increased maternal stress, trauma, difficult and/or impoverished environments, in tandem with genetic predispositions, can result in alterations to their neurodevelopment that predispose them to self-regulatory problems that can be expressed at any stage of life. The care of infants with Neonatal Abstinence Syndrome (NAS)/Neonatal Opioid Withdrawal Syndrome (NOWS) and their mother/caregiver is a window of opportunity to assess the regulatory and co-regulatory capacities of both, and to provide holistic interventions with the goal of empowering the mother/caregiver in their own self-knowledge/self-regulation capacities and their crucial role in promoting the healthy development of their children. Non-pharmacologic care for the infant with NAS/NOWS is the first line of treatment and of paramount importance. Yet, current approaches are based on a limited scope of infant functioning, and the scoring systems in current use do not result in individualized and specific non-pharmacologic care of the infant, which can result in excessive or insufficient medication and a lack of caregiver appreciation for the infant's strengths, difficulties and early development. The interventions described here are based on the infant's signs of dysregulation in four neurobehavioral subsystems that can be dysregulated by NAS/NOWS, the infant's adaptive or maladaptive responses to return to a regulated functioning, and the co-regulatory behaviors of the infant and the mother/caregiver. In Part I of this two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS we laid the foundation for a new treatment approach, one grounded in developmental theory and evidence-based observations of infant and interpersonal neurobiology. Here, in Part II, we outline actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on strategies to support the regulatory capacities and development of 4 key domains: 1) autonomic; 2) motor/tone; 3) sleep/awake state control; and 4) sensory modulation subsystems.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil.

Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension-anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger-hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.

Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications.

The incidence and prevalence of hypertension is increasing worldwide, with approximately 1.13 billion of people currently affected by the disease, often in association with other diseases such as diabetes mellitus, chronic kidney disease, dyslipidemia/hypercholesterolemia, and obesity. The autonomic nervous system has been implicated in the pathophysiology of hypertension, and treatments targeting the sympathetic nervous system (SNS), a key component of the autonomic nervous system, have been developed; however, current recommendations provide little guidance on their use. This review discusses the etiology of hypertension, and more specifically the role of the SNS in the pathophysiology of hypertension and its associated disorders. In addition, the effects of current antihypertensive management strategies, including pharmacotherapies, on the SNS are examined, with a focus on imidazoline receptor agonists.

Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats.

Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21-100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.

Impact of acute antioxidant supplementation on vascular function and autonomic nervous system modulation in young adults with PTSD.

Posttraumatic stress disorder (PTSD) has been associated with an increase in risk of cardiovascular disease (CVD). The goal of this study was to determine if peripheral vascular dysfunction, a precursor to CVD, was present in young adults with PTSD, and if an acute antioxidant (AO) supplementation could modify this potential PTSD-induced vascular dysfunction. Thirteen individuals with PTSD were recruited for this investigation and were compared with 35 age- and sex-matched controls (CTRL). The PTSD group participated in two visits, consuming either a placebo (PTSD-PL) or antioxidants (PTSD-AO; vitamins C and E; α-lipoic acid) before their visits, whereas the CTRL subjects only participated in one visit. Upper and lower limb vascular functions were assessed via flow-mediated dilation and passive leg movement technique. Heart rate variability was utilized to assess autonomic nervous system modulation. The PTSD-PL condition, when compared with the CTRL group, reported lower arm and leg microvascular function as well as sympathetic nervous system (SNS) predominance. After acute AO supplementation, arm, but not leg, microvascular function was improved and SNS predominance was lowered to which the prior difference between PTSD group and CTRL was no longer significant. Young individuals with PTSD demonstrated lower arm and leg microvascular function as well as greater SNS predominance when compared with age- and sex-matched controls. Furthermore, this lower vascular/autonomic function was augmented by an acute AO supplementation to the level of the healthy controls, potentially implicating oxidative stress as a contributor to this blunted vascular/autonomic function.

Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: role of autonomic nervous system.

BACKGROUND: To evaluate the effect of nicotinamide prior to streptozotocin-induced (STZ) diabetes in baroreflex sensitivity and cardiovascular autonomic modulation, and its association with hemodynamics and metabolic parameters. METHODS: Methods: Male Wistar rats were divided into control (Cont) and STZ-induced diabetes (Diab). Half of the rats from each group received a single dose of nicotinamide (100 mg/Kg) before STZ injection (Cont+NicA and Diab+NicA). All groups were followed-up for 5 weeks. RESULTS: Body weight loss of more than 40% was observed in Diab throughout the period (Diab: 271.00 ± 12.74 g; Diab+NicA: 344.62 ± 17.82). Increased glycemia was seen in Diab rats (541.28 ± 18.68 mg/dl) while Diab+NicA group had a slight decrease (440.87 ± 20.96 mg/dl). However, insulin resistance was observed only in Diab. In relation to Cont, heart rate, mean blood pressure and diastolic function were reduced when compared to Diab, together with parasympathetic modulation and baroreflex sensitivity. All of these parameters were improved in Diab+NicA when compared to Diab. Improved baroreflex sensitivity and parasympathetic modulation were correlated with glycemia, insulin resistance, and body weight mass. Additionally, Diab+NicA group increased survival rate. CONCLUSIONS: Results suggest that the association of nicotinamide in STZ-induced diabetic rats prevents most of the expected derangements mainly by preserving parasympathetic and baroreflex parameters.

Conditions of Aerogenic Exposure to Benzene and Genetic Status as Factors of Formation of Immune Profile Features in Men with Autonomic Regulation Disturbances.

We studied the immunological status and polymorphic variants of candidate genes in men with disturbances of autonomic nervous regulation under conditions of aerogenic exposure to benzene. The group of men with pathology of the autonomic nervous system (autonomic dysfunction syndrome) living under conditions of aerogenic exposure to benzene is characterized by increased blood contamination with benzene, which 1.5-fold surpassed this parameter in the group of conventionally healthy men (p<0.05). The immune profile of the surveyed men is characterized by increased specific sensitization (IgG to benzene) and activation of apoptosis (TNFR, p53) and phagocytosis. The production of serum IgA was also increased (p<0.05) in men of this group. The content of CD127- lymphocytes significantly (p<0.05) exceeded the reference level against the background of a significantly reduced (p<0.05) level of CD3+CD95+ lymphocytes irrespective of the presence or absence of autonomic nervous system pathology in men with excessive haptenic load with benzene. The revealed features of the immune status of men with autonomic regulation disorders were significantly associated (OR>1; p<0.05) with the variant allele of the FOXP3 immune regulation gene (rs3761547) and with wild-type allele of the SOD2 superoxide dismutase gene (rs2758330) and the corresponding homozygous genotypes. The established features of immune regulation (hyperproduction of IgG to benzene, imbalance of apoptosis markers (CD127-, CD3+CD95+, p53, and TNFR) against the background of altered polymorphism of candidate genes (FOXP3, SOD2) form a complex of genetic and immunological markers of autonomic regulation disorders in men living under conditions of aerogenic exposure to benzene.