Sympathetic Nervous System Overactivity Research Articles

Intradialytic Hypertension in Maintenance Hemodialysis.

To summarize the current evidence regarding epidemiology, clinical pathophysiology, and latest therapeutic approaches for the management of intradialytic hypertension (IDH). IDH is a rather common complication of dialysis, affecting 10-15% of the patient population and significantly increasing the cardiovascular risk. Its pathophysiology involves multiple mechanisms, including volume and sodium overload, sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) overactivity, endothelial dysfunction, and arterial stiffness. IDH management requires a combination of nonpharmacological and pharmacological interventions. The first mainly focus on volume control through dry weight optimization and modification of dialysate sodium, as studies show that strict volume control or low dialysate sodium can significantly reduce intradialytic and ambulatory blood pressure (BP). Pharmacological interventions have also been examined in research studies. Beta-blockers, particularly those with vasodilatory properties, can effectively target mechanisms such as SNS overactivity and endothelial dysfunction, and have shown some promising results reducing both intradialytic and ambulatory BP. Other drugs classes have also been explored as potential therapeutic options for IDH management, though further research is needed to clarify the efficacy of these interventions. A tailored approach addressing both the underlying pathophysiological mechanisms and individualized patient is warranted for improving BP control and cardiovascular outcomes in this high-risk population.

Sympathetic nerve promotes renal fibrosis by activating M2 macrophages through β2-AR-Gsa

Sympathetic nervous system overactivation is directly related to renal fibrosis. This study focused on the role of and mechanism by which sympathetic signaling regulates macrophage activation, as well as the contribution to renal fibrosis. Renal denervation alleviated tubular necrosis, tubulointerstitial fibrosis, and macrophage accumulation induced by unilateral ureteral obstruction and ischemia-reperfusion injury. In vitro, norepinephrine (NE) promoted macrophage alternative (M2) polarization by activating β2-adrenergic receptor (β2-AR) and heterotrimeric G stimulatory protein α-subunit (Gsa). The effects of NE-induced macrophage M2 polarization were blocked by a β2-AR selective antagonist and Gsa siRNA. Importantly, ablation of Gsa in macrophages alleviated tubulointerstitial fibrosis, macrophage accumulation, and M2 polarization in the renal ischemia-reperfusion injury model. Sympathetic nervous system overactivation regulates M2 polarization in macrophages as an important neuroimmune mechanism of renal fibrosis. The β2-AR-Gsa signaling pathway was responsible for NE-induced macrophage M2 polarization, which may be a therapeutic target for renal fibrosis.

Arrhythmogenic effects of DEHP exposure: insights into cardiac electrophysiology and myocardial cells

Abstract Introduction Hemodialysis patients, who are exposed to plasticizers through the hemodialysis circuit, face a high risk of cardiovascular disease (CVD). Plasticizers, such as the endocrine-disrupting compound Di(2-ethylhexyl) phthalate (DEHP), have emerged as potential contributors to CVD. This study explores the impact of DEHP on cardiac electrophysiology and myocardial cells, providing insights into its cardiotoxic effects. Methods We employed optical mapping techniques to assess cardiac electrophysiology in Langendorff-perfused rat hearts exposed to DEHP, comparing them to a control group. Additionally, we evaluated the effect of DEHP on cardiac muscle cells using H9C2 rat cardiomyoblasts. Results Prolonged DEHP exposure resulted in elevated heart rate, increased electrocardiographic variability, and higher low-frequency values, indicative of sympathetic nervous system overactivity. Action potential duration at APD80 increased, leading to greater action potential triangulation. Electrical alternans observed in the DEHP-treated group heightened the risk of arrhythmias. Single-cell analysis revealed severe mitochondrial damage, myocardial cell apoptosis, and disrupted calcium ion balance. Conclusion This study highlights DEHP's cardiotoxicity, suggesting its potential role in arrhythmogenesis and cardiac dysfunction. Environmental pollutants like DEHP warrant consideration as contributors to cardiovascular diseases, emphasizing the need for further research on preventive strategies.

Current approach to resistant hypertension

Resistant hypertension is the inability to achieve target blood pressure (<130/80 mmHg) despite using the maximum tolerated doses of three antihypertensive drugs, including a diuretic, or the need for four or more medications. It is linked to aging, obesity, obstructive sleep apnea, and chronic kidney disease, with contributing factors such as high sodium intake and sympathetic nervous system overactivity. Treatment includes optimizing diuretic use, with spironolactone proving highly effective. Lifestyle modifications, including sodium reduction and exercise, are critical. Emerging therapies like renal denervation offer promising long-term blood pressure control.

Impaired Neurocirculatory Control in Chronic Kidney Disease: New Evidence for Blunted Sympathetic Baroreflex and Reduced Sympathetic Transduction.

Chronic kidney disease (CKD) is characterized by over-activation of the sympathetic nervous system (SNS) that increases cardiovascular risk. Whether sympathetic baroreflex sensitivity (sBRS) is impaired or intact in CKD remains under-studied and controversial. Furthermore, the downstream effect of SNS activation on blood pressure transduction has not been previously examined in CKD. We tested the hypothesis that sBRS is attenuated, while sympathetic transduction is augmented in CKD. In 18 sedentary patients with CKD stages III-IV (eGFR: 40±14mL/min) and 13 age-matched controls (eGFR: 95±10mL/min), beat-to-beat blood pressure (BP; finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest for 10-min. Weighted linear regression analysis between MSNA burst incidence and diastolic BP was used to determine the spontaneous sBRS. Sympathetic-BP transduction was quantified using signal averaging, whereby the BP response to each MSNA burst was tracked over 15 cardiac cycles and averaged to derive the peak change in BP. Compared with controls, CKD patients had an attenuated sBRS [CKD: -1.34±0.59 versus CON: -2.91±1.09 bursts (100 heartbeats)-1 mmHg-1; P=0.001]. |sBRS| was significantly associated with eGFR (r=0.69, P<0.001). CKD patients had attenuated sympathetic-BP transduction compared to controls (0.75±0.7vs. 1.60±0.8mmHg; P=0.010). Resting MSNA was negatively associated with sympathetic transduction (r = -0.57, P=0.002). CKD patients exhibit impaired sBRS that may contribute to SNS overactivation and cardiovascular risk in this patient population. In addition, CKD patients had an attenuated sympathetic transduction that may counteract the vascular effects of SNS overactivation.

Exploring the Comorbidity, Pathophysiology, and Integrated Treatment Strategies of Hypertension and Depression

Hypertension and depression are widely prevalent conditions with substantial comorbidity. Hypertension, characterized by persistently elevated arterial pressure, is associated with significant cardiovascular morbidity and mortality. Depression, a multifactorial mood disorder, adversely affects mental and physical health through mechanisms involving neuroinflammation, neurotransmitter imbalances, and hormonal dysregulation. The association between these disorders has been recognized since the mid-20th century.Historical medical literature from ancient Chinese and Indian systems identified symptoms indicative of hypertension, later classified as a distinct disease entity by Fredrick Akbar Mahomed in the 19th century. Notable epidemiological studies have elucidated the significant relationship between hypertension and depression, particularly among medical students and other high-risk populations.Research indicates that common pathophysiological mechanisms, including sympathetic nervous system overactivity, chronic inflammation, and endothelial dysfunction, underlie the comorbidity of hypertension and depression. Elevated levels of norepinephrine, proinflammatory cytokines, and oxidative stress contribute to the expression or worsening of both conditions. Shared genetic and environmental factors further compound this relationship, highlighting the need for integrated treatment strategies.Pharmacological interventions, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have shown potential to improve mental health outcomes in patients with comorbid hypertension and depression. However, inconsistent findings regarding the impact of antihypertensive medications on depression necessitate further investigation. The comorbidity of these conditions complicates treatment adherence, leading to poorer health outcomes and increased healthcare costs.The clinical implications of this unidirectional or bidirectional comorbidity are considerable, affecting quality of life, treatment adherence, and overall health outcomes. Integrated care approaches, incorporating lifestyle modifications and combined pharmacological treatments, have shown promise in improving compliance and outcomes.Despite extensive research, limitations persist, including difficulties in establishing causality, inconsistent diagnostic criteria, and the influence of confounding variables. Future research should focus on clarifying the bidirectional relationship between these conditions, the impact of social determinants, and the efficacy of various treatment modalities. Identifying high-risk populations and refining intervention strategies are crucial for improving clinical outcomes in patients with comorbid hypertension and depression.This paper aims to review the current literature regarding the association and comorbidity of hypertension and depression.Abbreviations: ACE: Angiotensin-Converting Enzyme; ARBs: Angiotensin Receptor Blockers; DBP: Diastolic Blood Pressure; mm Hg: Millimeters of Mercury; QoL: Quality of Life; SBP: Systolic Blood Pressure

Sympathetic Transduction to Blood Pressure in Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is a major health problem affecting more than 35 million Americans. Notably, more patients with CKD die of cardiovascular complications than progress to end-stage renal disease. An overactive sympathetic nervous system is a well-known cardiovascular risk factor. Previous research has suggested elevated resting sympathetic nerve activity and a heightened α-adrenergic receptor sensitivity in patients with CKD, both of which may predispose this population to greater sympathetic transduction. Therefore, we tested the hypothesis that patients with stage III CKD have an augmented sympathetic transduction to blood pressure (BP) compared to controls without CKD. In 7 patients with stage III CKD and 8 controls muscle sympathetic nerve activity (MSNA; peroneal microneurography) and beat-to-beat BP (finometer) were continuously recorded during 10 minutes of quiet supine rest. Modelflow was used to estimate stroke volume and calculate total vascular conductance (TVC). Sympathetic transduction was quantified as the peak change in mean arterial pressure (MAP) and the nadir reduction of TVC over 10 cardiac cycles following spontaneous MSNA bursts using signal averaging. Patients with CKD and controls had similar resting MAP (CKD: 102 ± 14 mmHg; CON: 95 ± 8 mmHg; P = 0.27), MSNA burst frequency (CKD: 33 ± 10 bursts/min; CON: 31 ± 14 bursts/min; P = 0.78) and MSNA burst incidence (CKD: 53 ± 15 bursts/100 heartbeats; CON: 47 ± 24 bursts/100 heartbeats; P = 0.60). Peak increases in MAP following all bursts of MSNA were not different between patients with CKD and controls (CKD: 2.1 ± 0.7 mmHg; CON: 2.2 ± 0.9 mmHg; P = 0.83). Likewise, nadir reductions in TVC following all bursts of MSNA were not different in patients with CKD (CKD: -1.2 ± 0.6 ml/min/mmHg; CON: -1.4 ± 0.5 ml/min/mmHg; P = 0.46). Similar results were observed when considering burst patterning. MSNA bursts occurring in multiples (adjacent to other bursts) produced comparable peak MAP (CKD: 2.6 ± 0.6 mmHg; CON: 2.8 ± 1.2 mmHg; P = 0.67) and nadir TVC (CKD: -1.5 ± 0.7 ml/min/mmHg; CON: -1.9 ± 0.7 ml/min/mmHg; P = 0.25) responses between groups. There were also no differences in peak MAP and nadir TVC responses following single bursts of MSNA (bordered by cardiac cycles lacking bursts; both P &gt; 0.30). These preliminary data suggest that, in contrast to our hypothesis, sympathetic transduction to BP is not augmented in patients with stage III CKD. This project was supported by the National Heart, Lung, and Blood Institute R01 HL-127071 (PJF). 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.

Sex Differences in Hemodynamic and Autonomic Reactivity during Cold Pressor Test in Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is characterized by sympathetic nervous system (SNS) overactivity that contributes to increased cardiovascular risk. Hemodynamic reactivity during the cold pressor test (CPT) has been widely used to evaluate sympathetic neural control in patient populations, and increased neurocardiovascular reactivity to CPT has been shown to predict greater risk of future cardiovascular events. Prior studies have suggested that males with CKD have higher long-term cardiovascular disease risk compared to females with CKD; however, whether sex differences in neurocardiovascular responsivity during CPT exists within CKD remains unknown. Objectives: Our primary objective was to evaluate potential sex differences in hemodynamic and autonomic reactivity during CPT in patients with CKD. Hypothesis: Males with CKD have an augmented pressor and sympathetic response to sympathoexcitation induced by CPT compared with females with CKD. Methods: Patients with CKD (Stage III and IV) with stable renal function were included. Continuous beat to beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) by microneurography were measured at rest for 10 minutes and during CPT that consisted of immersion of the hand to the wrist in ice water (4–5 °C) for one minute, followed by a 5-min recovery period. Results: 25 participants with CKD were included (N= 14 male, N=11 female). There were no differences in baseline characteristics, resting hemodynamics or MSNA between male and female groups. Males with CKD had a steeper rate of increase and higher peak levels of diastolic BP (DBP, 101±3 vs 87±3; p=0.008) and mean arterial BP (MAP, 130±4 vs 112±5 mm Hg, p=0.023) during CPT compared to females with CKD, respectively. Conversely, females with CKD had a steeper rate of increase in HR during CPT compared to males. MSNA increased in both males and females during CPT; however, there was no difference in MSNA reactivity during CPT between groups. Conclusions: Males with CKD had greater BP reactivity during CPT compared to females with CKD, while females with CKD had greater HR reactivity during CPT compared to males. There was no difference in sympathetic reactivity between groups. Augmented BP reactivity during CPT in males with CKD may contribute to sex differences in cardiovascular disease risk in patients with CKD. Supported by NIH Grants R33AT010457 and R01HL135183. 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.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE &gt; 83%, n=17) and poor effciency (SE &lt; 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p&gt;0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p&gt;0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. 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.

Sex differences in sympathetic activity and pulse wave velocity in adults with chronic kidney disease.

Chronic kidney disease (CKD) is characterized by sympathetic nervous system (SNS) overactivity that contributes to increased vascular stiffness and cardiovascular risk. Although it is well established that SNS activity and vascular stiffness are substantially elevated in CKD, whether sex differences in autonomic and vascular function exist in CKD remains unknown. We tested the hypothesis that compared with females, males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness. One hundred twenty-nine participants (96 males and 33 females) with CKD stages III and IV were recruited and enrolled. During two separate study visits, vascular stiffness was assessed by measuring carotid-to-femoral pulse wave velocity (cfPWV), and resting muscle sympathetic nerve activity (MSNA) was measured by microneurography. Males with CKD had higher resting MSNA compared with females with CKD (68 ± 16 vs. 55 ± 14 bursts/100 heart beats, P = 0.005), whereas there was no difference in cfPWV between the groups (P = 0.248). Resting MSNA was not associated with cfPWV in both males and females. In conclusion, males with CKD have higher resting sympathetic activity compared with females with CKD. However, there was no difference in vascular stiffness between the sexes. There was no correlation between resting MSNA and cfPWV, suggesting that non-neural mechanisms may play a greater role in the progression of vascular stiffness in CKD, particularly in females.NEW & NOTEWORTHY Males with chronic kidney disease (CKD) have higher resting muscle sympathetic nerve activity (MSNA) compared with females. There was no correlation between MSNA and carotid-to-femoral pulse wave velocity (cfPWV), suggesting that non-neural mechanisms may play a greater role in the progression of vascular stiffness in CKD. Sex differences in SNS activity may play a mechanistic role in observations from epidemiological studies suggesting greater cardiovascular risk in males compared with females with CKD.

Autonomic nervous modulation: early treatment for pulmonary artery hypertension.

Pulmonary artery hypertension (PAH) is a chronic vascular disease defined by the elevation of pulmonary vascular resistance and mean pulmonary artery pressure, which arises due to pulmonary vascular remodelling. Prior research has already established a link between the autonomic nervous system (ANS) and PAH. Therefore, the rebalancing of the ANS offers a promising approach for the treatment of PAH. The process of rebalancing involves two key aspects: inhibiting an overactive sympathetic nervous system and fortifying the impaired parasympathetic nervous system through pharmacological or interventional procedures. However, the understanding of the precise mechanisms involved in neuromodulation, whether achieved through medication or intervention, remains insufficient. This limited understanding hinders our ability to determine the appropriate timing and scope of such treatment. This review aims to integrate the findings from clinical and mechanistic studies on ANS rebalancing as a treatment approach for PAH, with the ultimate goal of identifying a path to enhance the safety and efficacy of neuromodulation therapy and improve the prognosis of PAH.

Involvement of aquaporin 5 and Na-K-2Cl cotransporter 1 in the pathogenesis of primary focal hyperhidrosis: evidence from the primary sweat gland cell culture.

People with primary focal hyperhidrosis (PFH) usually have an overactive sympathetic nervous system, which can activate the sweat glands through the chemical messenger of acetylcholine. The role of aquaporin 5 (AQP5) and Na-K-2Cl cotransporter 1 (NKCC1) in PFH is still unknown. The relative mRNA and protein levels of AQP5 and NKCC1 in the sweat gland tissues of three subtypes of patients with PFH (primary palmar hyperhidrosis, PPH; primary axillary hyperhidrosis, PAH; and primary craniofacial hyperhidrosis, PCH) were detected with real-time PCR (qPCR) and Western blot. Primary sweat gland cells from healthy controls (NPFH-SG) were incubated with different concentrations of acetylcholine, and the relative mRNA and protein expression of AQP5 and NKCC1 were also detected. NPFH-SG cells were also transfected with si-AQP5 or shNKCC1, and acetylcholine stimulation-induced calcium transients were assayed with Fluo-3 AM calcium assay. Upregulated AQP5 and NKCC1 expression were observed in sweat gland tissues, and AQP5 demonstrated a positive Pearson correlation with NKCC1 in patients with PPH (r = 0.66, P < 0.001), patients with PAH (r = 0.71, P < 0.001), and patients with PCH (r = 0.62, P < 0.001). Upregulated AQP5 and NKCC1 expression were also detected in primary sweat gland cells derived from three subtypes of patients with PFH when compared with primary sweat gland cells derived from healthy control. Acetylcholine stimulation could induce the upregulated AQP5 and NKCC1 expression in NPFH-SG cells, and AQP5 or NKCC1 inhibitions attenuated the calcium transients induced by acetylcholine stimulation in NPFH-SG cells. The dependence of ACh-stimulated calcium transients on AQP5 and NKCC1 expression may be involved in the development of PFH.NEW & NOTEWORTHY The dependence of ACh-stimulated calcium transients on AQP5 and Na-K-2Cl cotransporter 1 (NKCC1) expression may be involved in the development of primary focal hyperhidrosis (PFH).

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF.

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

Catheter-based renal artery denervation: facts and expectations

Catheter-based renal artery denervation (RAD) is entering a new era. After the disappointing results of SYMPLICITY-HTN 3 trial in year 2014, several technical and methodological advancements led to execution of important SHAM-controlled randomized trials with promising results. Now, the 2023 ESH Guidelines give RAD a class of recommendation II with a Level of Evidence B. Currently, catheter-based RAD has two main areas of application: (a) Hypertensive patients who are still untreated, in whom RAD is a sort of a first-line treatment; (b) Difficult-to-control or true resistant hypertensive patients. Notably, randomized SHAM-controlled trials met their primary end-point in both these conditions. So far, we do not dispose of established predictors of the antihypertensive response to RAD. Some data suggest that younger patients with systo-diastolic hypertension, absence of diffuse atherosclerosis and evidence of sympathetic nervous system overactivity experience a better BP response to the procedure. We reviewed the available data on catheter-based RAD and included an updated meta-analysis of the results of the available SHAM-controlled trials. Overall, the reduction in 24-h systolic blood pressure (BP) after RAD exceeded that after SHAM by 4.58 mmHg (95% CI 3.07–6.10) in untreated patients, and by 3.82 mmHg (95% CI 2.46–5.18) in treated patients, without significant heterogeneity across trials, patient phenotype (untreated versus treated patients) and technique (radiofrequency versus ultrasound). There were no important safety signals related to the procedure. Notably, some data suggest that RAD could be an effective additional approach in patients with atrial fibrillation and other conditions characterized by sympathetic nervous system overactivity.

Sex differences in arterial stiffness and sympathetic activity in older CKD patients

Chronic kidney disease (CKD) is characterized by sympathetic nervous system overactivity that contributes to increased arterial stiffness and cardiovascular risk. While premenopausal females are relatively protected from cardiovascular disease in healthy individuals, older postmenopausal females without kidney disease have similar degrees of sympathetic overactivity, vascular stiffness and cardiovascular risk compared to older age-matched males in the general population. However, in the CKD population, cardiovascular mortality risk remains higher in older males compared to age-matched females and whether sex differences in neural and vascular function exist in older CKD patients is unknown. Therefore, we tested the hypothesis that compared to older females, older males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness. In 207 CKD patients (N=90 females, 62 ± 9 years; and N=117 males, 60 ± 9 years), we measured resting sympathetic nerve activity directed to muscle (MSNA) by microneurography at the peroneal nerve. At a separate visit, arterial stiffness was determined by carotid-to-femoral pulse wave velocity (PWV) using transcutaneous Doppler flow velocity (SphygmoCor®). Office blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM; Spacelabs) were performed using standard techniques. Resting MSNA was higher in males versus females with CKD (43 ± 10 vs 31 ± 14 bursts/min; p= 0.039). Both office and 24-hour ambulatory diastolic BP (79 ± 11 vs 67 ± 14 mmHg, p&lt;0.001) and mean arterial pressure (96 ± 10 vs 88 ± 13 mmHg, p&lt;0.001) were also higher in males versus females. PWV was not different between male and female groups (p= 0.157). There was no association between PWV and resting MSNA in males, while in females, there was an inverse relationship between PWV and MSNA burst frequency (r2=0.271; p=0.039) and burst incidence (r2=0.310; p=0.025). Older male CKD patients have higher resting MSNA, office and ambulatory BP compared to older females with CKD. In contrast, there were no differences in arterial stiffness measured as PWV between sexes. In males, increased MSNA was not associated with increased arterial stiffness, while MSNA was negatively correlated with PWV in females. Sex differences in neural and vascular function may impact cardiovascular outcomes in older patients with CKD. Supported by NIH grants R01HL135183, R33AT010457. This is the full abstract presented at the American Physiology Summit 2023 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.

Evidence of Sympathetic Overactivity in Subjects with REM Behavior Disorder at Risk for Parkinson’s Disease (P6-13.002)

<h3>Objective:</h3> To evaluate sympathetic nervous system (SNS) activity in subjects with REM sleep behavior disorder (RBD) at risk of Parkinson’s disease, using imaging and autonomic functions markers. <h3>Background:</h3> While the nature of RBD is not completely understood, there is evidence that enhancement of noradrenergic activity may play a causative role, as suggested by evidence of persistent tonic discharge of locus coeruleus (LC) and RBD-triggering action of selective norepinephrine reuptake inhibitors. <h3>Design/Methods:</h3> Subjects &gt;50 years old with RBD with at least one pre-motor PD symptom (hyposmia, constipation, depression) were tested with a battery of autonomic evaluations including SCOPA-AUT questionnaire, cardiac MIBG scintigraphy, Heart Rate Variability (HRV) and neuromelanin sensitive MRI (NSMRI) of LC and substantia nigra (SN). Analyzed variables included: 1) for MIBG, late heart/mediastinum (H/M) ratio and washout ratio (WR); 2) for HRV, time and frequency domain measures; 3) for NSMRI, contrast-to-noise ratio (CNR) between LC and pons and between substantia nigra (SN) and cerebral peduncles. Results were compared with available normative ranges. <h3>Results:</h3> 14 subjects (11M, age 66.2±8.2) were enrolled. Average total SCOPA-AUT score was increased (12.1±6.7 vs 8.8±5.4), with gastrointestinal (2.4±2.1 vs 1.4±1.6), urinary (5.4±2.7 vs 3.9±2.4) and cardiovascular (0.86±1.10 vs 0.3±0.6) scores above normal ranges. MIBG late H/M ratio was reduced (1.45±0.31) with increased WR (33.0±14.8). HRV results showed enhanced sympathetic and low parasympathetic activity both in time (SDNN 106.8±73.2ms; RMSSD 21.9±10.9ms; PNN50% 6.7±8.4%) and frequency domain (LF/HF 3.4±1.8). NMSMRI showed high LC CNR (right 3.26±1.9 vs 2.08±0.5; left 2.95±0.9 vs 2.79±0.5). SN CNR was high (Medial 6.24±1.9 vs 4.57±0.8; Central 6.26±1.6 vs 3.43±0.6; Lateral 3.44±2.1 vs 3.05±0.5) and MDS-UPDRS motor scores were low (2.9±3.3). <h3>Conclusions:</h3> RBD subjects at risk for PD show abnormal autonomic scores, which appears to be driven by SNS overactivity, as suggested by increased MIBG WR, elevated LF/HF HRV ratios and increased LC and SN NSMRI signal. <b>Disclosure:</b> Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boston Scientific. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDerm. Dr. Tagliati has received publishing royalties from a publication relating to health care. Dr. Gregorio has nothing to disclose. Dr. Maghzi has nothing to disclose. Gloria Obialisi has nothing to disclose. Dr. Hogg has nothing to disclose. Dr. Malatt has nothing to disclose. Dr. Tan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Dr. Artal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceuticals. Dr. Artal has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Private Parties. The institution of Dr. Artal has received research support from Jazz Pharma. The institution of Dr. Artal has received research support from Axsome. The institution of Dr. Artal has received research support from Suven. Dr. Shehata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Brian Renner has nothing to disclose. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care.

Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO-A and prevents cardiac remodeling in obese rats.

Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored. An obesity model was induced by 16-week high-fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3-L1 in transwell chambers were used to investigate the mechanisms. CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO-A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO-A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO-A inhibitor. CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO-A and prevents cardiac remodeling in obese rats.

A Case Report: Stellate Ganglion Blocks can help Alleviate Symptoms of Long COVID-19

Stellate Ganglion blocks have been used to alleviate a wide range of medical conditions due to an overactive sympathetic nervous system. There have been multiple case reports of patients who have undergone a stellate ganglion block after suffering from symptoms of Long COVID-19. Our case report demonstrates that a stellate ganglion block can be used as a treatment modality for symptoms of Long COVID-19. Future research should focus on optimizing the techniques behind the procedure including medication selection and laterality choice.

Osteopathic Findings and Treatment of Patient with Crohn’s Disease and Post-Ileocecal Resection: A Case Report

Abstract Crohn’s disease is a form of inflammatory bowel disease (IBD) that chronically damages the lining of the digestive tract. The symptoms of Crohn’s disease can vary secondary to its severity, ranging from asymptomatic patients to those suffering from constant abdominal pain, diarrhea, blood loss, and fatigue. Patients with Crohn’s disease endure a decreased quality of life depending on the extent of their symptoms. Crohn’s disease can be differentiated from other forms of IBD by its location in the gastrointestinal (GI) tract and distinct gross and microscopic morphology. This disease can affect any portion of the GI tract, but most commonly affects the terminal ileum and colon. The affected portion exhibits transmural inflammation, where all layers of the bowel are damaged, leading to strictures and fistulas. In this case of a patient with fistulizing fibro-stenotic Crohn’s disease, ileocecal resection was required. 1-week post-surgery, the patient suffered from continuous pain and discomfort with sympathetic nervous system overactivity. The somatic dysfunctions diagnosed on osteopathic structural examination were addressed with osteopathic manipulative treatment (OMT) and directed to restore the functionality of her sympathetic and parasympathetic nervous systems. The patient’s symptoms were found to have improved after the application of OMT. The results of this case study suggest that treating post-surgery patients using osteopathic techniques, specifically following ileocecal resection, can improve their post-op symptoms and reduce the need for post operative oral pain medications. Patient’s consent for this case report was obtained in written and verbal form.