Elevated Sympathetic Activity Research Articles

Connecting transcriptomics with computational modeling to reveal developmental adaptations in pediatric human atrial tissue.

Nearly 1% of babies are born with congenital heart disease-many of whom will require heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate drug therapies, and inform clinical care decisions related to surgical repair and postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we collected right atrial tissue samples from pediatric patients (n = 117) undergoing heart surgery. Patients were stratified into five age groups. We measured age-dependent adaptations in cardiac gene expression and used computational modeling to simulate action potential and calcium transients. Enrichment of differentially expressed genes revealed age-dependent changes in several key biological processes (e.g., cell cycle, structural organization), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited age-dependent trends, with changes in calcium handling (INCX) and repolarization (IK1) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We observed a shift in repolarization reserve, with lower IKr expression in younger patients, a finding potentially tied to an increased amplitude of IKs that could be triggered by elevated sympathetic activation in pediatric patients. Collectively, this study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology, shedding light on molecular mechanisms underlying cardiac maturation and function throughout development.NEW & NOTEWORTHY To date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is limited. In this study, we demonstrate age-dependent adaptations in the gene expression profile of >100 atrial tissue samples collected from congenital heart disease patients. We coupled transcriptomics datasets with computational modeling to simulate action potentials and calcium transients for different pediatric age groups.

Renal nerves in physiology, pathophysiology and interoception.

Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure. Increased renal sympathetic nerve activity is thought to contribute to hypertension by promoting renal sodium retention, renin release and renal vasoconstriction. This hypothesis led to the development of catheter-based renal denervation (RDN) for the treatment of hypertension. Two RDN devices that ablate both efferent and afferent renal nerves received FDA approval for this indication in 2023. However, in animal models, selective ablation of afferent renal nerves resulted in comparable anti-hypertensive effects to ablation of efferent and afferent renal nerves and was associated with a reduction in sympathetic nerve activity. Selective afferent RDN also improved kidney function in a chronic kidney disease model. Notably, the beneficial effects of RDN extend beyond hypertension and chronic kidney disease to other clinical conditions that are associated with elevated sympathetic nerve activity, including heart failure and arrhythmia. These findings suggest that the kidney is an interoceptive organ, as increased renal sensory nerve activity modulates sympathetic activity to other organs. Future studies are needed to translate this knowledge into novel therapies for the treatment of hypertension and other cardiorenal diseases.

Abstract P170: Angiotensin II Receptor Associated Protein Expression Within the PVN of Spontaneously Hypertensive Rats

Increased levels of circulating Angiotensin II (Ang II) have been linked to the development of neurogenic hypertension and elevated sympathetic activity, primarily through the Angiotensin II Receptor 1 (AT1R). Angiotensin II Receptor Associated Protein (ATRAP) is a transmembrane protein that regulates Ang II signaling by promoting the internalization of AT1R. Studies have demonstrated that in a model of Ang II-induced hypertension, enhancing ATRAP expression in the paraventricular nucleus of the hypothalamus (PVN) via Lentivirus infection reduced high blood pressure. However, whether ATRAP is differentially expressed in Spontaneously Hypertensive Rats (SHR) is unknown. We hypothesized that ATRAP gene and protein expression decreases during the development of hypertension in SHRs, leading to increased Ang II signaling. To test this, we used male SHRs at 4 (pre-hypertensive) and 12-weeks-old (wo, hypertensive; mean arterial pressure (MAP) 128.0±2.7 vs. 149.2±5.30 mmHg, respectively, measured by tail-cuff recording [Kent Scientific]) and age-matched normotensive Wistar rats (WIS, 92.6±3.3 vs. 123.6±4.6 mmHg, respectively). We measured ATRAP and AT1R mRNA expression in PVN samples using real-time PCR. Protein expression density of ATRAP was assessed using immunofluorescence (IF) and confocal imaging. We found no differences in ATRAP mRNA expression in the PVN between groups ( p >0.05). On the other hand, we found a significant increase in AT1R mRNA expression after hypertension is developed (WIS 12wo: 1.12 ± 0.35; vs. SHR 12wo: 4.17 ± 1.07, p =0.02). While no differences were found in ATRAP, using ATRAP/AT1R ratio as an indicator of AT1R overactivity and decrease in ratio after the development of hypertension (SHR 12wo: 0.23 ± 0.06 vs. WIS 12wo:1.05 ± 0.25) further indicate increased AngII signaling. As observed with ATRAP mRNA expression, no statistical differences were observed in ATRAP protein density within the SHR at 12wo as measured in a separate cohort of animals (MAP SHR 12wo:149.0 ± 3.7 vs. WIS 12wo:115.8 ± 4.0; p >0.05). These results suggest that the increased AngII signaling within the PVN of SHR are most likely due to increased AT1r expression rather than a differential expression of ATRAP. This work was partially funded by AHA 953524 to VCB.

Sedation Efficacy of Midazolam in Conjunction with Ketamine and Alfaxalone in Female Laboratory Guinea Pigs (Cavia porcellus).

Guinea pigs have been integral as models used in biomedical research, making significant contributions to nutritional, auditory, immunologic, and hypersensitivity studies, and necessitating the routine need for sedation in laboratory settings. The ketamine-xylazine (KX) combination has been the standard sedation protocol for decades. However, due to the adverse effects and abuse potential of xylazine, this study explores the possibility of substituting xylazine with midazolam and examines the combined use of midazolam with ketamine and alfaxalone in female laboratory guinea pigs. Our findings indicate that KX facilitates the fastest induction and longest duration of sedation compared with other sedatives, including ketamine-midazolam (KM), which, despite its rapid induction, results in significantly shorter sedation durations. KX also ensures a deeper anesthetic depth and greater odds of loss of withdrawal and inguinal reflexes, in contrast to KM and alfaxalone-midazolam (AM), under which only 15% of the animals lost these reflexes. In terms of cardiopulmonary function, KM led to an increased heart rate attributed to elevated sympathetic activity. All 4 sedative protocols lead to respiratory depression, except KM, which causes minimal reduction. Adverse events varied, with 75% of animals experiencing injection site reactions after KX administration and 67% exhibiting regurgitation post-KM administration. No adverse events were reported for the AM combination, suggesting its safer profile. In conclusion, while KX remains the superior protocol for sedation due to its efficiency, reliability, and minimal impact on physiologic parameters, midazolam is not a preferable alternative to replace xylazine. Its increased sympathetic tone, hyperesthesia, and shorter action duration, coupled with a higher potential for adverse events, limit its suitability to combine with ketamine in guinea pig sedation. However, when midazolam is used in conjunction with safer alternatives like alfaxalone, it presents a viable sedation strategy, emphasizing the need for further research into optimizing sedative combinations for laboratory guinea pigs.

Psychological distress, forced awakening, and morning blood pressure surge.

Morning blood pressure surge (MBPS) has been recognized as an independent predictor of cardiovascular disease events. Psychological distress, including anxiety, depression, and perceived stress, and behavioral risk factors, such as poor sleep quality, have been associated with increased MBPS. Elevations in sympathetic activity induced by forced awakening may also contribute to further increases in MBPS. Yet, no examination of the interrelationships among psychological distress, sleep quality, awakening mode (natural vs. forced awakenings), and MBPS has been undertaken. This pilot study aimed: (1) to examine if MBPS differs by awakening mode and (2) to investigate whether psychological distress is associated with MBPS difference between natural and forced awakenings, independent of sleep quality. Thirty-two healthy adults were included in this cross-sectional study. Blood pressure was measured using a beat-to-beat blood pressure monitor over two nights, consisting of one night of natural awakening and one night of forced awakening. Psychological distress and sleep quality were assessed using questionnaires. We conducted paired t-tests (aim 1) and multiple linear regressions (aim 2). MBPS was significantly greater during forced awakening compared with natural awakening. In addition, the MBPS difference between natural and forced awakenings was significantly greater in participants with higher anxiety levels, independent of sleep quality. We found that augmentation of MBPS by forced awakening was significantly greater in individuals who reported higher anxiety levels. Additional research is needed to examine the potential impacts of forced awakening and anxiety on MBPS in a larger sample of individuals at risk for cardiovascular disease.

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy

BackgroundObstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.Methods and resultsForty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.ConclusionsOSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.Trial registrationNCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125.

안마의자를 활용하는 마사지가 성인 남녀의 자율신경균형도에 미치는 즉각적 영향: 전향적 관찰연구

Objectives The aim of this study was to examine the immediate impact of a massage chair intervention on homeostasis and the balance of the autonomic nervous system in individuals aged 20 to 64. Methods This study was a single-center, prospective, single-arm, investigator-initiated observational study. Non-underweight adults without significant health concerns underwent a 40-minute massage chair intervention. Measurements of heart rate variability, functional near-infrared spectroscopy, and vital signs were conducted before and after the intervention. Additionally, participants completed the Mibyeong questionnaire and a satisfaction survey. Results A 40-minute massage chair session led to a notable decrease in average heart rate and low frequency to high frequency (LF/HF) ratio, coupled with an increase in root mean square of the successive differences (RMSSD) and standard deviation of NN interval (SDNN). No adverse reactions were noted. Subjects with elevated sympathetic nerve activity exhibited a reduction in LF/HF ratio, whereas those with heightened parasympathetic activity demonstrated an increase in LF/HF ratio post-intervention. Conclusions The findings indicate that the massage chair intervention has the potential to activate the parasympathetic nervous system, promote blood pressure homeostasis and autonomic nervous system balance. However, further research over a more extended period is crucial to validate these conclusions.

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia.

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2-80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

Oxytocin and corticotropin-releasing hormone exaggerate nucleus tractus solitarii neuronal and synaptic activity following chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) in rodents mimics the hypoxia-induced elevation of blood pressure seen in individuals experiencing episodic breathing. The brainstem nucleus tractus solitarii (nTS) is the first site of visceral sensory afferent integration, and thus is critical for cardiorespiratory homeostasis and its adaptation during a variety of stressors. In addition, the paraventricular nucleus of the hypothalamus (PVN), in part through its nTS projections that contain oxytocin (OT) and/or corticotropin-releasing hormone (CRH), contributes to cardiorespiratory regulation. Within the nTS, these PVN-derived neuropeptides alter nTS activity and the cardiorespiratory response to hypoxia. Nevertheless, their contribution to nTS activity after CIH is not fully understood. We hypothesized that OT and CRH would increase nTS activity to a greater extent following CIH, and co-activation of OT+CRH receptors would further magnify nTS activity. Our data show that compared to their normoxic controls, 10days' CIH exaggerated nTS discharge, excitatory synaptic currents and Ca2+ influx in response to CRH, which were further enhanced by the addition of OT. CIH increased the tonic functional contribution of CRH receptors, which occurred with elevation of mRNA and protein. Together, our data demonstrate that intermittent hypoxia exaggerates the expression and function of neuropeptides on nTS activity. KEY POINTS: Episodic breathing and chronic intermittent hypoxia (CIH) are associated with autonomic dysregulation, including elevated sympathetic nervous system activity. Altered nucleus tractus solitarii (nTS) activity contributes to this response. Neurons originating in the paraventricular nucleus (PVN), including those containing oxytocin (OT) and corticotropin-releasing hormone (CRH), project to the nTS, and modulate the cardiorespiratory system. Their role in CIH is unknown. In this study, we focused on OT and CRH individually and together on nTS activity from rats exposed to either CIH or normoxia control. We show that after CIH, CRH alone and with OT increased to a greater extent overall nTS discharge, neuronal calcium influx, synaptic transmission to second-order nTS neurons, and OT and CRH receptor expression. These results provide insights into the underlying circuits and mechanisms contributing to autonomic dysfunction during periods of episodic breathing.

Exercise Pressor Reflex Function Is Exacerbated in Decerebrate Adenine-Induced Chronic Kidney Disease Rats

Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD). While the underlying mechanisms are not completely understood, elevated sympathetic nerve activity (SNA) and exercise intolerance are thought to play an important role. In normal physiological conditions, sympathetic modulation of the cardiovascular system during physical activity is largely governed by a peripheral neural reflex originating in contracting skeletal muscle, known as the exercise pressor reflex (EPR). Pioneering work by Park et al. demonstrated that CKD patients exhibited abnormal SNA and blood pressure (BP) elevations during both static and rhythmic handgrip exercise, suggesting an overactive EPR. However, due to experimental design constraints inherent to humans, the contribution of the EPR to the augmented SNA and BP responses to exercise could not be fully addressed. Therefore, the purpose of this study was to specifically test EPR function in CKD using a reduced animal model. Sprague-Dawley rats were randomly assigned to receive either a powdered chow diet containing adenine (0.25%w/w in feed) to induce CKD or a powdered chow diet alone (control group) for 12 weeks. Subsequently, in decerbrate animals, we measured mean arterial pressure (MAP) and renal SNA (RSNA) in response to isolated EPR activation during hindlimb muscle contraction (i.e., simulated exercise). We further assessed cardiovascular and sympathetic responses to passive muscle stretch to stimulate the mechanoreflex (i.e., activation of the mechanically-sesnsitive component of the EPR), and intra-arterial capsaicin administratration to activate the metaboflex (i.e., stimulation of the metabolically-sensitive component of the EPR). After completion of the diet, levels of plasma creatinine were significantly increased in adenine-fed rats compared to control rats (2.57±1.05 vs. 0.34±0.05 mg/dL, P&lt;0.01), suggesting impaired renal function (i.e., adenine-induced CKD). We found that CKD animals exhibited augmentations in RSNA (Δ=153±75 vs. 61±50 %, P&lt;0.05) and MAP (Δ=35±18 vs. 17±8 mmHg, P&lt;0.05) in response to muscle contraction when compared to control animals. Importantly, the muscle tension developed during contraction was similar between the two groups (Δ=0.9±0.2 vs. 1.0±0.3 kg, P&gt;0.1, CKD vs. control). During stimulation of the mechanoreflex, CKD rats also exhibited significantly greater RSNA (Δ=100±54 vs. 32±26 %, P&lt;0.05) and MAP responses (Δ=25±14 vs. 10±7 mmHg, P&lt;0.05) than control rats. The developed muscle tension during passive stretch was similar between the two groups (Δ=0.9±0.2 vs. 1.0±0.4 kg, P&gt;0.1, CKD vs. control). There was a tendency for the responses to metaboreflex activation to be heightened in the CKD group compared with the control group, but the difference did not reach statistical significance (ΔRSNA=212±68 vs. 107±105 %, P=0.06, ΔMAP=67±12 vs. 48±21 mmHg, P=0.06, CKD vs. control, respectively). Our findings suggest that EPR function, particularly muscle mechanoreflex function, is exaggerated in CKD, leading to sympathetic activation and hypertensive responses during exercise. P30 DK079307 Subaward to H.K. and R01HL-133179 to W.V. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Skeletal muscle contractions attenuate the norepinephrine-related reduction in interstitial oxygen pressures in the rat spinotrapezius

Increased sympathetic nerve activity with exercise plays a key role in the control of arterial blood pressure and redistribution of blood flow. Within the microcirculation, elevated sympathetic outflow promotes the release of norepinephrine and smooth muscle contraction. Exercise-induced attenuation of sympathetic vasoconstriction (i.e., functional sympatholysis) is thus critical for active muscle oxygen delivery-utilization matching. However, the extent to which muscle contractions impact noradrenergic regulation of interstitial oxygen pressures (PO2is) is unknown. This is important because, as dictated by Fick’s law, PO2is provides the sole driving force for oxygen diffusion into the myocyte thereby supporting oxidative phosphorylation. PURPOSE: To determine the effects of norepinephrine administration on resting and contracting rat skeletal muscle PO2is. We tested the hypothesis that topical application (superfusion) of norepinephrine would result in blunted decreases in skeletal muscle PO2is during contractions compared to rest. METHODS: PO2is was determined via phosphorescence quenching in the exposed spinotrapezius muscle of anesthetized male Sprague-Dawley rats (n=7, 2-3 months old) at rest and during electrically-induced submaximal contractions (0.5 Hz, 3-6 V) for 6 minutes in response to norepinephrine superfusion (5x10−4 M). Functional sympatholysis was determined as the difference between the norepinephrine-induced changes in PO2is at rest and during the contraction steady-state (i.e., 2 min following the onset of muscle contractions) using (i) the absolute PO2is fall with norepinephrine (ΔPO2is), and (ii) the area under the PO2is curve plotted as a function of time (AUC). The tail (caudal) artery was cannulated for measurements of mean arterial pressure (MAP) and heart rate (HR). RESULTS: Consistent with our hypothesis, skeletal muscle contractions attenuated norepinephrine-evoked reductions in spinotrapezius interstitial oxygenation as evaluated by ΔPO2is (rest: -8.7±1.4, contractions: -4.3±1.1 mmHg, p&lt;0.05) and AUC (rest: 2246±368, contractions: 1066±273 mmHg·s, p&lt;0.05). Although MAP increased significantly with norepinephrine both at rest (+5±1%, p&lt;0.05) and during contractions (+8±1%, p&lt;0.05), this mild hypertensive response to norepinephrine was not different between conditions (p&gt;0.05). Norepinephrine superfusion did not affect HR at rest or during contractions (p&gt;0.05). CONCLUSIONS: That muscle contractions blunted the decrease in spinotrapezius PO2is with norepinephrine compared to the resting condition is consistent with functional sympatholysis. The latter serves to match active muscle O2 delivery-utilization in the face of elevated sympathetic nerve activity during exercise. The current results indicate that a novel combination of phosphorescence quenching (interstitial oxygenation, PO2is) and superfusion techniques may be used to evaluate functional sympatholysis in the intact rat spinotrapezius muscle. Showalter Research Trust, Purdue University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of sex and sedentary conditions on sympathetic burst characteristics in prepubertal, postpubertal, and young adult rats.

Recent evidence indicates that sex-based differences in cardiovascular disease (CVD) begin early in life, particularly when associated with risk factors such as a sedentary lifestyle. CVD is associated with elevated sympathetic nerve activity (SNA), quantified as increased SNA burst activity in humans. Whether burst characteristics are influenced by sex or sedentary conditions at younger ages is unknown. The purpose of our study is to compare SNA bursts in active and sedentary female and male rats at ages including prepuberty and young adulthood. We hypothesized that burst characteristics and blood pressure are higher under sedentary conditions and lower in female rats compared with males. We analyzed splanchnic SNA (SpSNA) recordings from Inactin-anesthetized male and female rats at 4-, 8-, and 16-wk of age. Physically active and sedentary rats were each housed in separate, environmentally controlled chambers where physically active rats had free access to an in-cage running wheel. Sympathetic bursts were obtained by rectifying and integrating the raw SpSNA signal. Burst frequency, burst height, and burst width were calculated using the Peak Parameters extension in LabChart. Our results showed that sedentary conditions produced a greater burst width in 8- and 16-wk-old rats compared with 4-wk-old rats in both males and females (P < 0.001 for both). Burst frequency and incidence were both higher in 16-wk-old males compared with 16-wk-old females (P < 0.001 for both). Our results suggest that there are sedentary lifestyle- and sex-related mechanisms that impact sympathetic regulation of blood pressure at ages that range from prepuberty into young adulthood.NEW & NOTEWORTHY The mechanisms of decreased incidence of cardiovascular disease (CVD) in reproductive-age women compared with age-matched men are unknown. The strong association between elevated sympathetic activity and CVD led us to characterize splanchnic sympathetic bursts in female and male rats. Prepubescent males and females exhibited narrower sympathetic bursts, whereas young adult males had higher resting burst frequency compared with age-matched females. Sex-based regulation of sympathetic activity suggests a need for sex-dependent therapeutic strategies to combat CVD.

Acute combined effects of concurrent physical activities on autonomic nervous activation during cognitive tasks.

Backgrounds: The validity of heart rate variability (HRV) has been substantiated in mental workload assessments. However, cognitive tasks often coincide with physical exertion in practical mental work, but their synergic effects on HRV remains insufficiently established. The study aims were to investigate the combined effects of cognitive and physical load on autonomic nerve functions. Methods: Thirty-five healthy male subjects (aged 23.5 ± 3.3years) were eligible and enrolled in the study. The subjects engaged in n-back cognitive tasks (1-back, 2-back, and 3-back) under three distinct physical conditions, involving isotonic contraction of the left upper limb with loads of 0kg, 3kg, and 5kg. Electrocardiogram signals and cognitive task performance were recorded throughout the tasks, and post-task assessment of subjective experiences were conducted using the NASA-TLX scale. Results: The execution of n-back tasks resulted in enhanced perceptions of task-load feelings and increased reaction times among subjects, accompanied by a decline in the accuracy rate (p < 0.05). These effects were synchronously intensified by the imposition of physical load. Comparative analysis with a no-physical-load scenario revealed significant alterations in the HRV of the subjects during the cognitive task under moderate and high physical conditions. The main features were a decreased power of the high frequency component (p < 0.05) and an increased low frequency component (p < 0.05), signifying an elevation in sympathetic activity. This physiological response manifested similarly at both moderate and high physical levels. In addition, a discernible linear correlation was observed between HRV and task-load feelings, as well as task performance under the influence of physical load (p < 0.05). Conclusion: HRV can serve as a viable indicator for assessing mental workload in the context of physical activities, making it suitable for real-world mental work scenarios.

Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat.

Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex. We recorded the arterial pressure and renal sympathetic nerve activity (RSNA) response to epicardial bradykinin application in anesthetized SHR and Wistar Kyoto (WKY) rats before and after PVN microinjection of GABA A agonist muscimol or ionotropic glutamate receptor antagonist kynurenic acid. Muscimol significantly decreased the arterial pressure response to bradykinin from 180.4 ± 5.8 to 119.5 ± 6.9 mmHg in the SHR and from 111.8 ± 7.0 to 84.2 ± 8.3 mmHg in the WKY and the RSNA response from 186.2 ± 7.1 to 142.7 ± 7.3% of baseline in the SHR and from 201.0 ± 11.5 to 160.2 ± 9.3% of baseline in the WKY. Kynurenic acid significantly decreased the arterial pressure response in the SHR from 164.5 ± 5.0 to 126.2 ± 7.7 mmHg and the RSNA response from 189.9 ± 13.7to 168.5 ± 12.7% of baseline but had no effect in the WKY. These results suggest that tonic PVN activity is critical for the full manifestation of the CSAR in both the WKY and SHR. Glutamatergic PVN activity contributes to the augmented CSAR observed in the SHR.

Is polycystic ovary syndrome associated with elevated muscle sympathetic nerve activity?

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities, cardiometabolic disturbances and a heightened risk of cardiovascular disease. A small but compelling body of research demonstrates that females with PCOS present with elevated muscle sympathetic nerve activity (MSNA) at rest. Heightened MSNA is present in lean, overweight and obese females with PCOS, but limited evidence suggests that androgens may be more strongly linked to elevated MSNA in lean females with PCOS than in obese females with PCOS. Although the specific mechanisms underlying elevated MSNA in PCOS remain elusive, sympathetic activation is implicated in the progression of several cardiovascular diseases and may contribute to the cardiovascular pathophysiology of PCOS. Encouragingly, MSNA appears responsive to non-pharmacological intervention, making the sympathetic nervous system a promising therapeutic target to mitigate cardiovascular risk in PCOS. This brief review summarizes the existing evidence regarding elevated MSNA, cardiovascular risk profile and vascular function, as well as the potential for clinical intervention and future research directions in females with PCOS. NEW FINDINGS: What is the topic of this review? The presence of elevated muscle sympathetic nerve activity in females with polycystic ovary syndrome and the implications for cardiovascular health. What advance does it highlight? The sympathetic nervous system likely contributes to elevated cardiovascular disease risk in females with polycystic ovary syndrome. Moreover, it presents as a promising therapeutic target for mitigating cardiovascular disease and merits further investigation.

Assessment of Frontal Hemispherical Lateralization in Plaque Psoriasis and Atopic Dermatitis

Background: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization between the frontal hemispheres may provide insight into specific connections between skin diseases and the psyche. This study aims to analyze the hemispherical lateralization, neurovegetative responses, and psychometric characteristics of patients with Pso and AD. Methods: The study included 46 patients with Pso, 56 patients with AD, and 29 healthy control (Ctrl) subjects. The participants underwent frontal electroencephalogram (EEG) measurement, heart rate variability (HRV) assessment, and psychological tests. Statistical analyses were performed using ANOVA, with Bonferroni correction applied for multiple comparisons. Results: This study shows a significant right-lateralized prefrontal activity in both AD patients (p &lt; 0.001) and Pso patients (p = 0.045) compared with Ctrl, with no significant difference between the AD and Pso groups (p = 0.633). AD patients with right-hemispheric dominant prefrontal activation exhibited increased inhibition and avoidance markers, while Pso patients showed elevated sympathetic nervous system activity. Conclusion: Psychophysiological and psychometric data suggest a shared prevalence of right-hemispheric dominance in both AD and Pso patient groups. However, the findings indicate distinct psychodermatological mechanisms in AD and Pso.

Sympathoinhibitory electroacupuncture (EA) interacts positively with anti-inflammatory EA alleviating blood pressure in hypertensive rats.

Elevated sympathetic activity and chronic inflammation are known contributory factors observed in hypertension. We have observed that sympathoinhibitory electroacupuncture (SI-EA) at acupoints ST36-37 alleviates sympathetic activity and hypertension. Additionally, EA at acupoints SP6-7 exerts anti-inflammatory (AI-EA) effects. However, it is not known whether simultaneous stimulation of this combination of acupoints attenuates or enhances individual effects. A 2 × 2 factorial design was used to test the hypothesis that combining SI-EA and AI-EA (cEA) leads to greater reduction of hypertension by decreasing sympathetic activity and inflammation in hypertensive rats than either set of acupoints alone. Dahl salt-sensitive hypertensive (DSSH) rats were treated with four EA regimens including cEA, SI-EA, AI-EA, and sham-EA twice weekly for five weeks. A group of normotensive (NTN) rats served as control. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were measured non-invasively by tail-cuff. Plasma norepinephrine (NE), high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) concentrations were determined with ELISA at the completion of treatments. DSSH rats on high salt diet progressively developed moderate hypertension within five weeks. DSSH rats treated with sham-EA showed continuous increase in SBP and DBP and elevations in plasma NE, hs-CRP, and IL-6 levels relative to NTN control. Both SI-EA and cEA decreased SBP and DBP, and had corresponding changes in biomarkers (NE, hs-CRP, and IL-6) compared with sham-EA. AI-EA prevented SBP and DBP elevation and decreased IL-6 and hs-CRP relative to sham-EA. Importantly in DSSH rats that received repetitive cEA treatment, SI-EA interacted positively with AI-EA leading to greater reduction of SBP, DBP, NE, hs-CRP, and IL-6 than SI-EA or AI-EA alone. These data suggest that by targeting both elevated sympathetic activity and chronic inflammation, cEA regimen results in a greater reduction of BP effects in treating hypertension compared to using individual SI-EA or AI-EA alone.

Skin sympathetic nerve activity and nocturnal blood pressure nondipping in patients with postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is associated with abnormal blood pressure (BP) regulation and increased prevalence of nocturnal nondipping. We hypothesized that nocturnal nondipping of BP is associated with elevated skin sympathetic nerve activity (SKNA) in POTS. We used an ambulatory monitor to record SKNA and electrocardiogram from 79 participants with POTS (36 ± 11 years, 72 women), including 67 with simultaneous 24-h ambulatory BP monitoring. Nocturnal nondipping of BP was present in 19 of 67 (28%) participants. The nondipping group had a higher average SKNA (aSKNA) from midnight of day 1 to 0100 h on day 2 than the dipping group ( P = 0.016, P = 0.030, respectively). The differences (Δ) of aSKNA and mean BP between daytime and night-time were more significant in the dipping group compared with the nondipping group (ΔaSKNA 0.160 ± 0.103 vs. 0.095 ± 0.099 μV, P = 0.021, and Δmean BP 15.0 ± 5.2 vs. 4.9 ± 4.2 mmHg, P < 0.001, respectively). There were positive correlations between ΔaSKNA and standing norepinephrine (NE) (r = 0.421, P = 0.013) and the differences between standing and supine NE levels ( r = 0.411, P = 0.016). There were 53 (79%) patients with SBP less than 90 mmHg and 61 patients (91%) with DBP less than 60 mmHg. These hypotensive episodes were associated with aSKNA of 0.936 ± 0.081 and 0.936 ± 0.080 μV, respectively, which were both significantly lower than the nonhypotensive aSKNA (1.034 ± 0.087 μV, P < 0.001 for both) in the same patient. POTS patients with nocturnal nondipping have elevated nocturnal sympathetic tone and blunted reduction of SKNA between day and night. Hypotensive episodes were associated with reduced aSKNA.

Association Between Arterial Stiffness and Measures of Autonomic Dysfunction in People With Chronic Kidney Disease.

Autonomic nervous system (ANS) dysfunction and vascular stiffness increase cardiovascular risk in people with chronic kidney disease (CKD). Chronic elevations in sympathetic activity can lead to increased arterial stiffness; however, the relationship between these variables is unknown in CKD. To explore the association between measures of autonomic function and arterial stiffness in patients with moderate-to-severe CKD. This study was a prespecified secondary analysis of a randomized controlled trial. This included the following measures: 24-hour ambulatory blood pressure (BP), carotid-femoral and carotid-radial pulse wave velocity (PWV), and postexercise heart rate recovery (HRR). We used mixed effect linear regression models with Bayesian information criteria (BIC) to assess the contribution of ANS measurements. Forty-four patients were included in the analysis. Mean carotid-femoral and carotid-radial PWV were 7.12 m/s (95% CI 6.13, 8.12) and 8.51 m/s (7.90, 9.11), respectively. Mean systolic dipping, calculated as percentage change in mean systolic readings from day to night, was 10.0% (95% CI 7.79, 12.18). Systolic dipping was independently associated with carotid-radial PWV, MD -0.09 m/s (95% CI -0.15, -0.02) and had the lowest BIC. Systolic dipping was associated with carotid-radial PWV in people with moderate-to-severe CKD; however, there was no association with carotid-femoral PWV. Systolic dipping may be a feasible surrogate of ANS function, as the association with carotid-radial PWV was consistent with the minimal clinically important difference (MCID). Future studies are needed to define the relationship between ANS function, arterial stiffness, and CV events over time in people with CKD.

PS-B10-8: BLOCKADE OF AT1 RECEPTORS RESTORE P2/P1 WITHOUT CHANGING INTRACRANIAL PRESSURE IN RENOVASCULAR HYPERTENSIVE RATS WITH 0.3 M NACL AD LIBITUM

Objective: Renovascular hypertension is characterized by activation of the renin angiotensin aldosterone system, elevated sympathetic nerve activity and sodium appetite behavior. The association of increased sodium intake and hypertension can worsen the injury to end organs. We tested the effects of AT1 receptors blockade (losartan, 10 mg/kg iv) on mean arterial pressure (MAP), intracranial pressure (ICP) and P2/P1 ratio (index of brain compliance) in 2K1C rats with 0.3 M NaCl ad libitum. Design and Methods: Male Holtzman rats (150 tp 180 g) with water and food ad libitum received a silver clip around the left renal artery to induce 2K1C or no clip (SHAM surgery) resulting 3 groups: SHAM (n = 9), 2K1C (n = 9) and 2K1C/Na (n = 7), which had an additional bottle of 0.3 M NaCl ad libitum. Six weeks after the renal surgery, MAP and ICP were recorded under urethane anesthesia (1.2 g/kg iv) and the P2/P1 was calculated offline from the waveform. Saline (0.2 ml/rat) was used as control injection before losartan. Results: In SHAM rats, ICP and P2/P1 were not changed by losartan (7.8 ± 1.1 and 0.88 ± 0.02; vs. saline: 7.9 ± 1.1 and 0.83 ± 0.01 mmHg, respectively), while MAP was decreased (104 ± 5, vs. saline: 120 ± 3 mmHg, p &lt; 0.05). In 2K1C, MAP, ICP and P2/P1 values were greater than SHAM (respectively, 196 ± 6, 14.7 ± 2.7 and 1.1 ± 0.03 mmHg, vs. SHAM; p &lt; 0.05) and all of them were decreased by losartan pre-treatment (137 ± 6, 8.6 ± 1.3 and 0.87 ± 0.05 mmHg, vs. saline, respectively). In 2K1C-Na MAP and P2/P1 were greater than in SHAM (186 ± 7 and 1.15 ± 0.06 mmHg, vs sham p &lt; 0.05) and were decreased by losartan (162 ± 8 and 0.87 ± 0.02 mmHg, vs. saline; p &lt; 0.05), although the decrease in MAP after losartan was lesser than the observed in 2K1C rats (p &lt; 0.05). In 2K1C-Na rats, ICP was not different from SHAM (10.8 ± 1.2, vs. SHAM: 7.8 ± 1.1 mmHg, p &gt; 0.05) and losartan had no effect on ICP (10.3 ± 1.7, vs. saline: 10.8 ± 1.2 mmHg, p &gt; 0.05). Conclusion: Even without a change in ICP, AT1 blockade in 2K1C-Na was effective in restoring P2/P1 ratio, suggesting a beneficial effect on brain compliance in this situation.