Sympathetic Nervous System Overactivity Research Articles

RENAL FUNCTIONAL RESERVE IS RELATED TO THE NON-DIPPING PHENOTYPE AND TO THE EXERCISE HEART RATE RESPONSE IN PATIENTS WITH ESSENTIAL HYPERTESION AND A PRESERVED RENAL FUNCTION

Objective: Renal functional reserve (RFR) defined as the difference between stress and resting glomerular filtration rate (GFR) may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. A blunted RFR has been demonstrated in early stages of hypertension and has been attributed to an impaired vascular reactivity due to an overactive sympathetic nervous system. The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing an over-activity of the SNS in patients with essential hypertension and a preserved renal function. Design and method: Thirty-six patients with untreated essential hypertension and a GFR >60 ml/min/1.73m2 were enrolled. The following parameters were measured: RFR, a 24 h ambulatory BP profile, a treadmill stress test and an echocardiographic examination. Urine and venous samples were obtained for the determination of clinical parameters and calculation of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR below 30 ml/min/1.73m2 and 15 had a RFR above this cut-off. A non-dipping pattern of 24 h BP was significantly more frequent in patients with low RFR (57.1% vs. 25.0%, p < 0.05 for systolic BP and 52.3% vs 10.0%, p < 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate response to exercise during treadmill test (r = 0.439, p < 0.05). None of the echocardiographic parameters differed between the two groups of patients. Conclusions: In hypertensive patients with a preserved GFR, a reduced RFR is related to non-dipping BP phenotype as well as with an attenuated exercise HR response. An overactivity of the sympathetic nervous may be a common pathway. Since a loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with a blunted RFR might need a more careful renal follow-up.

The Effect of Stress Using Long-Term Continuous LightExposure on Liver Cells in Male and Female Wistar Rats

AbstractBackground: Many modern lifestyles are unhealthy andcan negatively affect our health. Many studies showed thatthe stress caused pronounced action on the structure of variousbody systems. The liver is one of the body organs that can beheavily affected by stress. The liver can withstand stress forlonger periods and shows signs of damage very late althoughthe structural changes can be detected very early.Aim of Study: Is to examine the acute and chronic effect of acute and chronic stress of long-term continuous light exposure on the structure of the liver tissues.Material and Methods: 48 male and female Wistar rats (250-300g) were enrolled in 6 groups (n=8/group). Group (a);Normal male control group with normal light/dark exposure.Group (b); Normal female control group with normal light/darkexposure. Group (c); Continuous room light for 3 weeks malegroup as an acute stress model in which normally fed malerats exposed to continuous room light exposure for 3 weeks.Group (d); Continuous room light for 3 weeks female groupas an acute stress model in which normally fed female ratsexposed to continuous room light exposure for 3 weeks.Group (e); Continuous room light for 3 months male groupas a chronic stress model in which normally fed male ratsexposed to continuous light exposure for 3 months. Group (f); Continuous room light for 3 months female group as achronic stress model in which normally fed female rats exposed to continuous light exposure for 3 months.Results: Sections of liver tissues of the groups who livedunder acute stress showed generally, preserved hepatic archi-tecture. The hepatocytes showed marked ballooning (vacuolardegeneration). The sinusoids and central veins showed con-gestion. Sections of liver tissues of the groups who livedunder chronic stress conditions showed in general, preservedhepatic architecture. The hepatocytes showed ballooning (vacuolar degeneration), focal spotty necrosis, together withsome binucleated cells. The sinusoids & central vein showedcongestion.Conclusion: This study used 48 Wistar mice as a modelto assess the effect of stress on liver tissues. Continuous roomlight exposure was used as acute stress for 3 weeks and aschronic stress for 3 months. This stressful stimulus and its deleterious effect on the liver may be supported by the theoryof sympathetic nervous system overactivity. The examinedliver tissues in this study showed congestive and degenerativechanges both in acute and chronic stressed animals. Changingmodern lifestyles to one that respects the natural chronobiologyis important for our wellbeing.

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

Purpose Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. Materials and methods Patients with TRH were randomised to RDN (n = 9) or Drug Adjustment (DA) (n = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation. Results CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs2 in the DA group vs. 1628µs2 in the RDN group, p = 0.03) with a clear tendency of reduction in the RDN group to 743µs2 after six months (p = 0.07), compared to no change in the DA group (1052µs2, p = 0.39). Conclusion Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516

Nocturnal blood pressure is associated with sympathetic nerve activity in patients with chronic kidney disease.

Elevated nocturnal blood pressure (BP) and nocturnal non‐dipping are frequently observed in patients with chronic kidney disease (CKD) and are stronger predictors of cardiovascular complications and CKD progression than standard office BP. The sympathetic nervous system (SNS) is thought to modulate diurnal hemodynamic changes and the vascular endothelium plays a fundamental role in BP regulation. We hypothesized that SNS overactivity and endothelial dysfunction in CKD are linked to elevated nocturnal BP and non‐dipping. In 32 CKD patients with hypertension (56 ± 7 years), office BP, 24‐hr ambulatory BP, muscle sympathetic nerve activity (MSNA) and endothelial function via flow‐mediated dilation (FMD) were measured. Participants were subsequently divided into dippers (nighttime average BP > 10% lower than the daytime average BP, n = 8) and non‐dippers (n = 24). Non‐dippers had higher nighttime BP (p < .05), but not office and daytime BP, compared to dippers. MSNA burst incidence (81 ± 13 versus 67 ± 13 bursts/100 HR, p = .019) was higher and brachial artery FMD (1.7 ± 1.5 versus 4.7 ± 1.9%, p < .001) was lower in non‐dippers compared to dippers. MSNA and FMD each predicted nighttime systolic (β = 0.48,‐0.46, p = .02, 0.07, respectively) and diastolic BP (β = 0.38,‐0.47, p = .04, 0.03, respectively) in multivariate‐adjusted analyses. Our novel findings demonstrate that unfavorable nocturnal BP profiles are associated with elevated SNS activity and endothelial dysfunction in CKD. Specifically, CKD patients with higher nighttime BP and the non‐dipping pattern have higher MSNA and lower FMD. These support our hypothesis that SNS overactivation and endothelial dysfunction are linked to the dysregulation of nighttime BP as well as the magnitude of BP lowering at nighttime in CKD.

Impact of Snoring on the Cardiovascular System and its Treatment: Positive and Negative Effects of Continuous Positive Airway Pressure in Sleep Apnea.

Obstructive sleep apnea (OSA) is a common condition, and if not treated can be a significant risk factor for multiple comorbidities like hypertension (HTN), coronary artery disease (CAD), and congestive heart failure (CHF). The underlying pathophysiology involves coagulation and inflammatory pathways, including an overactive sympathetic nervous system. This ultimately causes hemodynamic changes and subclinical myocardial injuries. We reviewed the published literature about the impact of continuous positive airway pressure (CPAP) when used as a mode of treatment to reduce the OSA effects on cardiomyocytes. We found that the results were mixed, including both ill and good effects. The cardiac markers like N-terminal pro-brain natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) were reduced, implying the decrease in the incidence of heart failure with CPAP treatment in a few of the studies. They also proved a significant decrease in harmful cardiovascular (CV) outcomes, while others concluded that CPAP therapy might be stressful on the heart, causing an elevation in cardiac troponin T levels. However, the impact on inflammatory markers is still indeterminate and needs more research in future.

Symptom Management Among Cancer Survivors: Randomized Pilot Intervention Trial of Heart Rate Variability Biofeedback.

Chronic cancer-related symptoms (stress, fatigue, pain, depression, insomnia) may be linked with sympathetic nervous system over-activation and autonomic imbalance. Decreased heart rate variability (HRV) is an indicator of autonomic dysregulation that is commonly observed among cancer survivors. HRV biofeedback (HRVB) training induces HRV coherence, which maximizes HRV and facilitates autonomic and cardiorespiratory homeostasis. This randomized, wait-list-controlled, pilot intervention trial tested the hypothesis that HRVB can improve HRV coherence and alleviate cancer-related symptoms. The intervention group (n = 17) received 4-6 weekly HRVB training sessions until participants demonstrated skill acquisition. Controls (n = 17) received usual care. Outcomes assessed at baseline and follow-up included 15-min HRV recordings (HRV Coherence Ratio), and symptoms of: stress, distress, post-traumatic stress disorder (PTSD), pain, depression, fatigue, and sleep disturbance. Linear mixed models for repeated measures were used to assess Group-by-Time interactions, pre- versus post-treatment differences in mean symptom scores, and group differences at follow-up. Mean HRV Coherence Ratios (± standard error) improved in the HRVB group at follow-up (baseline: 0.37 ± 0.05, post-intervention: 0.84 ± 0.18, p = 0.01), indicating intervention validity. Statistically significant Group-by-Time interactions indicated treatment-related improvements in HRV Coherence Ratios (p = 0.03, Pre-vs. post-treatment effect size [Cohen's d]: 0.98), sleep symptoms (p = 0.001, d = 1.19), and sleep-related daytime impairment (p = 0.005, d = 0.86). Relative to controls, the intervention group experienced trends toward improvements in stress, distress, fatigue, PTSD, and depression, although no other statistically significant Group-by-Time interactions were observed. This pilot intervention found that HRVB training reduced symptoms of sleep disturbance among cancer survivors. Larger-scale interventions are warranted to further evaluate the role of HRVB for managing symptoms in this population. Registration: NCT03692624 www.clinicaltrials.gov.

RENAL DENERVATION REGULATES LIPID METABOLISM THROUGH AMPK/PGC-1α PATHWAY IN DIET-INDUCED OBESE RATS

Sympathetic nervous system over-activity is closely linked with lipid metabolism disorder. Renal denervation (RDN) decreases systemic sympathetic nervous activity effectively, but little research has been done on the association between RDN and lipid metabolism. The purpose of this study was to

Obesity-related hypertension: a review of pathophysiology, management, and the role of metabolic surgery

Obesity is a significant public health challenge worldwide and is inextricably linked to adverse cardiovascular outcomes. The relationship between excess adiposity and increased blood pressure is well established, and it is estimated that obesity accounts for 65-78% of cases of primary hypertension. The mechanisms through which obesity causes hypertension are complex and include sympathetic nervous system overactivation, stimulation of the renin-angiotensin-aldosterone system, alterations in adipose-derived cytokines, insulin resistance, and structural and functional renal changes. Weight loss is the primary goal of treatment for obesity-related hypertension, although few individuals achieve success with nonpharmacological management alone. Specific considerations apply when selecting the most appropriate pharmacological therapy for obese hypertensive patients. Metabolic surgery has proved to be the most effective means of ensuring substantial and sustained weight loss and has also been shown to confer beneficial effects in type 2 diabetes mellitus. Increasing evidence suggests that metabolic surgery may also be an effective treatment for obesity-related hypertension, although prospective data on long-term blood pressure outcomes are awaited. This review will discuss the pathophysiological mechanisms that link obesity with hypertension and will provide an overview of treatment strategies, with a focus on metabolic surgery.

Sympathetic Activation in Hypertensive Chronic Kidney Disease - A Stimulus for Cardiac Arrhythmias and Sudden Cardiac Death?

Studies have revealed a robust and independent correlation between chronic kidney disease (CKD) and cardiovascular (CV) events, including death, heart failure, and myocardial infarction. Recent clinical trials extend this range of adverse CV events, including malignant ventricular arrhythmias and sudden cardiac death (SCD). Moreover, other studies point out that cardiac structural and electrophysiological changes are a common occurrence in this population. These processes are likely contributors to the heightened hazard of arrhythmias in CKD population and may be useful indicators to detect patients who are at a higher SCD risk. Sympathetic overactivity is associated with increased CV risk, specifically in the population with CKD, and it is a central feature of the hypertensive state, occurring early in its clinical course. Sympathetic hyperactivity is already evident at the earliest clinical stage of CKD and is directly related to the progression of renal failure, being most pronounced in those with end-stage renal disease. Sympathetic efferent and afferent neural activity in kidney failure is a crucial facilitator for the perpetuation and evolvement of the disease. Here, we will revisit the role of the feedback loop of the sympathetic neural cycle in the context of CKD and how it may aggravate several of the risk factors responsible for causing SCD. Targeting the overactive sympathetic nervous system therapeutically, either pharmacologically or with newly available device-based approaches, may prove to be a pivotal intervention to curb the substantial burden of cardiac arrhythmias and SCD in the high-risk population of patients with CKD.

Renal denervation restrains the inflammatory response in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored. First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a "two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate sympathoexcitation, and a 45-min ligation of the left coronary artery to induce myocardial I/R injury. The effects of RDN on the mobilization of immune cells in mice following myocardial I/R injury were explored. We observed a strong association between SNS overactivation and myeloid cell excessive accumulation in patients. In animal experiments, there was a significant reduction in infarct size per area at risk in the denervated-I/R group when compared to that of the innervated-I/R group (39.2% versus 49.8%; p < 0.005), and RDN also improved the left ventricular ejection fraction by 20% after 1week. Furthermore, the denervated-I/R group showed a decrease in the number of neutrophils and macrophages in the blood and the myocardium as reflected by immunohistochemical staining and flow cytometry analysis (p < 0.05); the decrease was associated with a significant reduction in the circulating production of IL-1, IL-6 and TNF-α (p < 0.05). In summary, our study reveals a novel link between the SNS activity and inflammatory response undergoing myocardium I/R injury and identifies RDN as a potential therapeutic strategy against myocardium I/R injury via preserving the spleen immune cells mobilization.

Bolest nealkoholne masne jetre kao metabolička posledica opstruktivne apneje u snu

Obstructive sleep apnea (OSA) as a worldwide prevalent condition carries risk for cardiovascular and metabolic diseases, ultimately increasing overall mortality rates. Non-alcoholic fatty liver disease (NAFLD) can be considered as the primary metabolic disease, but also as a coexisting OSA comorbidity. Although prevalence of NAFLD covers quarter of world population, it increases with OSA presence. It can be speculated that chronic intermittent hypoxia (CIH) and sympathetic nervous system overactivity are involved in NAFLD pathogenesis and progression from simple steatosis through steatohepatitis to fibrosis. CIH provides the environment for liver oxidative stress, inflammation and increases the expression of genes involved in cholesterol and fatty acids synthesis. Catecholamines increase b-oxidation in liver and release free fatty acids from adipose tissue in plasma which inhibit insulin effects. Obesity and insulin resistance as key players in NAFLD development and advancement, deepen vicious circle of oxidative stress, inflammation and dyslipidemia. If not treated, OSA in NAFLD patients has been associated with inflammation, hepatocytes' necrosis, and fibrosis. Continuous positive airway pressure (CPAP) represents gold standard for OSA therapy, allowing the unimpeded air passage through upper parts of respiratory system. However, it has been demonstrated that CPAP therapy have beneficial effects on cardiometabolic outcomes and slow liver degeneration.

Renal Functional Reserve Is Related to the Nondipping Phenotype and to the Exercise Heart Rate Response in Patients with Essential Hypertension and Preserved Renal Function

Background: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). Objective: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. Methods: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m² were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR <30 mL/min/1.73 m² and 15 had a RFR above this cutoff. A nondipping pattern of 24-h BP was significantly more frequent in patients with low RFR (57.1 vs. 25.0%, p < 0.05 for systolic BP and 52.3 vs. 10.0%, p < 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate (HR) response to exercise during treadmill test (r = 0.439, p < 0.05). None of the echocardiographic parameters differed between the two groups of patients. Conclusions: In hypertensive patients with preserved GFR, reduced RFR is related to nondipping BP phenotype as well as to attenuated exercise HR response. Overactivity of the SNS may be a common pathway. Since loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with blunted RFR might need a more careful renal follow-up.

Hypertension and sympathetic nervous system overactivity rely on the vascular tone of pial vessels of the rostral ventrolateral medulla in spontaneously hypertensive rats.

What is the central question of this study? Is purinergic signalling in the pial vessels involved in the control of vascular tone in the ventral surface of the brainstem, affecting high blood pressure and sympathetic overactivity in spontaneously hypertensive rats? What is the main finding and its importance? The regulation of vascular tone in the ventral surface of the brainstem is tailored to support neuronal functions, arterial pressure and sympathetic activity. This adds one more piece in the complex puzzle to understand the central mechanisms underlying the genesis of hypertension. Evidence suggests the rostral ventrolateral medulla (RVLM) region is chronically hypoperfused and hypoxic in spontaneously hypertensive rats (SHR), which can facilitate ATP release throughout the brainstem. Thus, we hypothesized that purinergic signalling plays a key role in the increased vascular tone in the RVLM region, which in turn could be responsible for the high sympathetic tone and blood pressure in the SHR. The application of an antagonist of P2 receptors, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (10µm), or of P2Y1a receptors, MRS2179 (100µm), on the surface of RVLM pial vessels of SHR produced an increase in the diameter of blood vessels (PPADS: 31±1.4µm or MRS2179: 32±0.78µm vs. saline: 27±1.2µm), an effect not observed in normotensive Wistar rats. In addition, the antagonism of P2 receptors was able to evoke a significant decrease in the arterial pressure, heart rate and splanchnic nerve activity in SHR, but not in Wistar rats. Our data show that SHR have higher vascular tone of pial vessels in the RVLM region when compared to the normotensive Wistar rats, a mechanism that relies on purinergic signalling through P2 receptors, suggesting a possible association with higher activity of sympathoexcitatory neurones, and sustained increases in blood pressure.

Circadian-timed quick-release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus.

ObjectiveSympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine‐QR, a dopamine‐agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine‐QR's effects on RHR and HbA1c in type 2 diabetes subjects.Design and SubjectsRHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine‐QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR).ResultsIn subjects with bRHR ≥70 beats/min, bromocriptine‐QR vs placebo reduced RHR by −3.4 beats/min and reduced BP (baseline 130/79; systolic, diastolic, mean arterial BP reductions [mm Hg]: −3.6 [P = .02], −1.9 [P = .05], −2.5 [P = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (−2.7 [P = .03], −5 [P = .002], −6.1 [P = .002] with bHbA1c ≤7, >7, ≥7.5%, respectively] in the bRHR ≥70 group and more so with bRHR ≥80 (−4.5 [P = .07], −7.8 [P = .015], −9.9 [P = .005]). Subjects with bRHR <70 had no significant change in RHR or BP. With bHbA1c ≥7.5%, %HbA1c reductions with bromocriptine‐QR vs placebo were −0.50 (P = .04), −0.73 (P = .005) and −1.22 (P = .008) with bRHR <70, ≥70 and ≥80, respectively. With bRHR ≥70, the magnitude of bromocriptine‐QR‐induced RHR reduction was an independent predictor of bromocriptine‐QR's HbA1c lowering effect.ConclusionBromocriptine‐QR lowers elevated RHR with concurrent decrease in BP and hyperglycaemia. These findings suggest a potential sympatholytic mechanism contributing to bromocriptine‐QR's antidiabetes effect and potentially its previously demonstrated effect to reduce CVD events.

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD)

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ± 2 beats/min) than in Controls (67 ± 2 beats/min) but comparable to M-PTSD (70 ± 3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ± 1 ms/mmHg) compared to controls (16 ± 3 ms/mmHg) but comparable to M-PTSD (12 ± 2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.

Improving obesity and blood pressure.

Obesity-associated hypertension is a serious public health concern. Sympathetic nervous system (SNS) overactivity, especially in the kidneys, is an important mechanism linking obesity to hypertension. Some adipokines play important roles in elevating blood pressure (BP). Hyperinsulinemia caused by insulin resistance stimulates sodium reabsorption, enhances sodium retention, and increases circulating plasma volume. Hyperinsulinemia also stimulates both the renin-angiotensin-aldosterone system (RAAS) and the SNS, resulting in the acceleration of atherosclerosis through the hypertrophy of vascular smooth muscle cells, which contributes to increased peripheral vascular resistance. Obesity is associated with increased RAAS activity despite volume overload, as the tissue RAASs are stimulated in obese hypertensive individuals. Mineralocorticoid receptor-associated hypertension must also be considered in obese patients with resistant hypertension. Obstructive sleep apnea syndrome (OSAS) is the most common cause of secondary hypertension. Some components of the gut microbiota contribute to BP control; therefore, gut dysbiosis caused by obesity might lead to increased BP. The ratio of visceral fat to subcutaneous fat is higher in Japanese patients than in Caucasian patients, which may explain why Japanese patients are more susceptible to metabolic disorders even though they are less obese than Caucasian individuals. Obesity-associated kidney dysfunction directly increases BP, leading to further deterioration of kidney function. A bodyweight reduction of more than 3% or 5 kg significantly lowers BP. Gastrointestinal bypass surgery is an effective treatment for morbid obesity and its related metabolic disorders, including hypertension. Because both obesity and hypertension are representative lifestyle-related disorders, lifestyle modification, especially to improve obesity, should be performed first as a treatment for hypertension.

Elevated airflow can maintain sleep quality and thermal comfort of the elderly in a hot environment.

The effect of elevated airflow on sleep quality was investigated with 18 elderly. Three airflow conditions were set: ceiling fan/30°C/max.0.8m/s and mean 0.7m/s, task fan/30°C/max.0.8m/s and mean 0.6m/s, and thermally neutral /27°C/0.2m/s. Sleep quality was evaluated objectively by analysis of electroencephalogram signals that were continuously monitored during the sleeping period. Urinary cortisol concentrations were analyzed to measure the activity of sympathetic nervous system. No significant difference in sleep quality, thermal comfort, or cortisol concentration was found between the ceiling fan and the neutral condition. The duration of total sleep time decreased by 35minutes, the duration of REM sleep decreased by 15minutes, and the cortisol concentration in the morning increased by 50ng/mL in the task fan than the other two conditions. Compared with ceiling fan, less heat load was removed in the task fan condition, possibly due to the lower air speed. This study shows that even small heat load led to reduced sleep quality and overactive sympathetic nervous system of the elderly. By supplying an airflow of 0.8m/s evenly over the human body, the elderly could maintain sleep quality and thermal comfort at an air temperature that was 3K higher than the neutral temperature.

2025 - RHEUMATOID ARTHRITIS INCREASES SYMPATHETIC NERVOUS SYSTEM DRIVEN HEMATOPOIETIC STEM CELL MOBILISATION AND ATHEROGENESIS

Rheumatoid arthritis (RA) patients have an increased risk for cardiovascular disease (CVD), independent of traditional risk factors such as plasma cholesterol levels. Interestingly, RA patients have elevated activity of the sympathetic nervous system (SNS), which has been known to play an important role in producing and releasing hematopoietic stem and progenitor cells (HSPCs) to produce inflammatory monocytes, the major contributor to atherosclerotic-CVD. Here we investigated whether increased atherosclerotic progression in mice with RA was due to SNS overactivity. We administered 8wk old C57/B6 mice with KBxN serum to elicit RA and found that RA mice had elevated blood HSPCs and myeloid (monocytes/neutrophils) levels. Further investigation of the bone marrow (BM) revealed an expansion of the HSPC pool, with a strong skewing towards myeloid progenitors, explaining the elevation in blood myeloid populations. Sympathetic activity levels, indicated by tyrosine staining, was also increased in the BM of RA mice. Administering RA mice with propanolol (b1/b2 receptor antagonist) and SR59230A (b3 receptor antagonist) to block SNS activity, led to a reduction in blood HSPC and myeloid populations. To explore the role of RA in atherogenesis we fed Ldlr-/- mice a high fat/high cholesterol diet for 14wks to stimulate lesion development. Mice were then switched to a normal chow diet for 3 weeks to allow lesion regression. Mice were injected with KBxN and treated with or without b-blockers. Mice injected with KBxN had impaired lesion regression which was prevented with b-blockers, likely due to a reduction in HSPC mobilisation and myeloid expansion. Therefore, targeting the SNS in patients with RA with b-blockers may reduce the risk for CVD.

Bucindolol Modulates Cardiac Remodeling by Attenuating Oxidative Stress in H9c2 Cardiac Cells Exposed to Norepinephrine.

The increased circulation of norepinephrine, found in the diseased heart as a result of sympathetic nervous system overactivation, is responsible for its cardiotoxic effects including pathological hypertrophy, cell death, and oxidative stress. Bucindolol is a third generation adrenergic blocker, which acts on the β1 and β2 receptors, and has additional α1 antagonist activity. Thus, the aim of this study was to investigate the action of bucindolol on oxidative stress, hypertrophy, cell survival, and cell death signaling pathways in H9c2 cardiac cells exposed to norepinephrine. H9c2 cells were incubated with 10 μM norepinephrine for 24 h in the presence or absence of bucindolol (10 μM) treatment for 8 h. Western blot was used to determine the expression of proteins for hypertrophy/survival and death signaling pathways. Flow cytometry was used to assess cell death via caspase-3/7 activity and propidium iodide and reactive oxygen species via measuring the fluorescence of CM-H2DCFDA. Norepinephrine exposure resulted in an increase in oxidative stress as well as cell death. This was accompanied by an increased protein expression of LC3B-II/I. The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. In conclusion, bucindolol was able to modulate cardiac remodeling which is mediated by oxidative stress.

COULD PLASMA ADRENALINE DURING COLD PRESSOR TEST BE USED TO IDENTIFY PATIENTS WHO RESPOND TO RENAL DENERVATION?

Objective:Sympathetic nervous system over-activity is associated with development- and maintenance of essential hypertension. Renal denervation (RDN) has been shown to lower both office- and ambulatory blood pressure (BP) in selected patients. Of 9 patients who underwent RDN we identified two patien