Pub Date : 2025-08-01Epub Date: 2025-04-12DOI: 10.1016/j.autneu.2025.103280
Gabriel do Carmo Silva , Maycon Junior Ferreira , Amanda Aparecida Araujo , Antonio Viana do Nascimento Filho , Nathalia Bernardes , Jônatas Bussador do Amaral , Maria Cláudia Irigoyen , Kátia De Angelis
<div><div>Antihypertensive drug and exercise training are commonly prescribed to treat arterial hypertension. However, there is a considerable gap in understanding how physiological mechanisms of male and female adapt to the combination of these approaches. Therefore, we focused to investigate sexual differences in cardiovascular, autonomic, inflammation and systemic oxidative stress adaptations in male and OVX female ovariectomized spontaneously hypertensive rats (SHR) treated with enalapril associated with moderate-intensity concurrent exercise training. Enalapril (3 mg/kg, diluted in drinking water) and exercise training (3 days/week, moderate intensity) was carried out for 8 weeks. Blood pressure (BP), heart rate (HR) and its variabilities were assessed. Serum and plasma were used for inflammatory and oxidative stress analyses. Enalapril, associated or not with exercise training, induced a reduction in diastolic and mean BP in both sexes; however, only the OVX female groups showed a reduction in systolic BP, as well as resting bradycardia. Both sexes showed improvements in BP and HR variability following the treatments; however, improvement in SD2/SD1 ratio, which indicates how much the heartbeats occur at irregular intervals, and in variance of systolic BP were observed only in trained groups. A higher spontaneous baroreflex sensitivity, as well as reduced IL-6/IL-10 were found only in the trained groups. Increased IL-10 was observed in male trained group (vs. other groups). Finally, combination enalapril and exercise training reduced systemic pro-oxidants such as NADPH oxidase and hydrogen peroxide. The findings of our study showed that OVX female SHR, after ovarian hormone deprivation, presented more pronounced effects on hemodynamics, BP variability, and anti-inflammatory profile than hypertensive males with the combination of treatments.</div></div><div><h3>Background</h3><div>Researchers are investigating how the body responds differently in males and females. These differences are also evident when examining how pharmacological and non-pharmacological approaches help the body control arterial hypertension. This study aimed to investigate how drug medication combined with exercise affects the heart's ability to self-regulate and how it relates to immune and oxidant defense, with a focus on differences in male and ovariectomized (OVX) female adaptations.</div></div><div><h3>Methods</h3><div>The study was conducted using hypertensive male and OVX female rats, allocated into: a) sedentary, b) enalapril, or c) enalapril plus exercise groups, totaling six groups (3 males and 3 OVX females, respectively). Enalapril (3 mg/kg/day) and exercise (aerobic and resistance exercises) were prescribed for eight weeks. The effects on blood pressure control, serum, and plasma were assessed.</div></div><div><h3>Results</h3><div>Although both males and OVX females showed improvements in blood pressure after medication, combined or not with exercise, OVX fe
{"title":"Cardiovascular and neuroimmune adaptations to enalapril and exercise training: A comparative study in male and ovariectomized female spontaneously hypertensive rats","authors":"Gabriel do Carmo Silva , Maycon Junior Ferreira , Amanda Aparecida Araujo , Antonio Viana do Nascimento Filho , Nathalia Bernardes , Jônatas Bussador do Amaral , Maria Cláudia Irigoyen , Kátia De Angelis","doi":"10.1016/j.autneu.2025.103280","DOIUrl":"10.1016/j.autneu.2025.103280","url":null,"abstract":"<div><div>Antihypertensive drug and exercise training are commonly prescribed to treat arterial hypertension. However, there is a considerable gap in understanding how physiological mechanisms of male and female adapt to the combination of these approaches. Therefore, we focused to investigate sexual differences in cardiovascular, autonomic, inflammation and systemic oxidative stress adaptations in male and OVX female ovariectomized spontaneously hypertensive rats (SHR) treated with enalapril associated with moderate-intensity concurrent exercise training. Enalapril (3 mg/kg, diluted in drinking water) and exercise training (3 days/week, moderate intensity) was carried out for 8 weeks. Blood pressure (BP), heart rate (HR) and its variabilities were assessed. Serum and plasma were used for inflammatory and oxidative stress analyses. Enalapril, associated or not with exercise training, induced a reduction in diastolic and mean BP in both sexes; however, only the OVX female groups showed a reduction in systolic BP, as well as resting bradycardia. Both sexes showed improvements in BP and HR variability following the treatments; however, improvement in SD2/SD1 ratio, which indicates how much the heartbeats occur at irregular intervals, and in variance of systolic BP were observed only in trained groups. A higher spontaneous baroreflex sensitivity, as well as reduced IL-6/IL-10 were found only in the trained groups. Increased IL-10 was observed in male trained group (vs. other groups). Finally, combination enalapril and exercise training reduced systemic pro-oxidants such as NADPH oxidase and hydrogen peroxide. The findings of our study showed that OVX female SHR, after ovarian hormone deprivation, presented more pronounced effects on hemodynamics, BP variability, and anti-inflammatory profile than hypertensive males with the combination of treatments.</div></div><div><h3>Background</h3><div>Researchers are investigating how the body responds differently in males and females. These differences are also evident when examining how pharmacological and non-pharmacological approaches help the body control arterial hypertension. This study aimed to investigate how drug medication combined with exercise affects the heart's ability to self-regulate and how it relates to immune and oxidant defense, with a focus on differences in male and ovariectomized (OVX) female adaptations.</div></div><div><h3>Methods</h3><div>The study was conducted using hypertensive male and OVX female rats, allocated into: a) sedentary, b) enalapril, or c) enalapril plus exercise groups, totaling six groups (3 males and 3 OVX females, respectively). Enalapril (3 mg/kg/day) and exercise (aerobic and resistance exercises) were prescribed for eight weeks. The effects on blood pressure control, serum, and plasma were assessed.</div></div><div><h3>Results</h3><div>Although both males and OVX females showed improvements in blood pressure after medication, combined or not with exercise, OVX fe","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103280"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-03-25DOI: 10.1016/j.autneu.2025.103271
E.L. Williams , J. Lando , V.-E.M. Lucci , B.C.D. Hockin , K. Elabd , S.N. Robinovitch , I.T. Parsons , V.E. Claydon
Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.
We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.
All discreet CPM augmented orthostatic SV (p < 0.001) and CO (p < 0.001), while reducing TPR (p < 0.001). SAP increased during AP (p < 0.001) and GC (p < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (p = 0.002) and SV (p = 0.022) that may predispose syncope. Only AP improved mMCAv (p = 0.005) and sympathovagal balance (p < 0.001). Responses were largest in those with greater initial cardiovascular instability (p < 0.003), larger leg muscle mass (p < 0.02), and where TPL was greater (p < 0.002).
These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.
{"title":"Orthostatic cardiovascular responses to postural sway and discreet counterpressure maneuvers","authors":"E.L. Williams , J. Lando , V.-E.M. Lucci , B.C.D. Hockin , K. Elabd , S.N. Robinovitch , I.T. Parsons , V.E. Claydon","doi":"10.1016/j.autneu.2025.103271","DOIUrl":"10.1016/j.autneu.2025.103271","url":null,"abstract":"<div><div>Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.</div><div>We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.</div><div>All discreet CPM augmented orthostatic SV (<em>p</em> < 0.001) and CO (<em>p</em> < 0.001), while reducing TPR (<em>p</em> < 0.001). SAP increased during AP (<em>p</em> < 0.001) and GC (<em>p</em> < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (<em>p</em> = 0.002) and SV (<em>p</em> = 0.022) that may predispose syncope. Only AP improved mMCAv (<em>p</em> = 0.005) and sympathovagal balance (<em>p</em> < 0.001). Responses were largest in those with greater initial cardiovascular instability (<em>p</em> < 0.003), larger leg muscle mass (<em>p</em> < 0.02), and where TPL was greater (<em>p</em> < 0.002).</div><div>These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103271"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-22DOI: 10.1016/j.autneu.2025.103292
Agnieszka Uryga , Marek Czosnyka , Magdalena Kasprowicz , Małgorzata Burzyńska , Barbara Dragan , Karol Budohoski , Nathalie Nasr
Background
Baroreflex sensitivity (BRS) is associated with clinical outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH); however few studies have investigated this in typical clinical settings. This two-centre study evaluated how outcome models differ when excluding patients who received beta-blockers and/or noradrenaline (‘clean data’ set) versus including all of them (‘noisy data’ set).
Methods
This retrospective study included consecutive aSAH patients from Addenbrooke's Hospital (UK) and Wroclaw Medical University (Poland). Early BRS was measured using the cross-correlation method. A favorable outcome was defined as a Glasgow Outcome Scale (GOS) score of 4–5 at discharge.
Results
A total of 108 patients were included, with 40 receiving beta-blockers and/or noradrenaline. The median age was 56 (IQR ± 17) years old, where 73 % were women. On admission, 57 % had a Glasgow Coma Scale (GCS) score of 13–15. Univariate logistic regression showed BRS was significantly associated with outcome in both the ‘clean data’ set (OR 1.16, 95%CI [1.02,1.30]) and ‘noisy data’ set (OR 1.10, 95%CI [1.03,1.18]). In multivariate analysis, the best ‘clean data’ model (χ2 = 22.89, p < 0.001, AUC = 0.88) included heart rate (HR) (OR 0.93, 95%CI [0.87,0.99]) and GCS (OR 1.38, 95%CI [1.12,1.69]). The best ‘noisy data’ model (χ2 = 32.27; p < 0.001, AUC = 0.84) included BRS (OR 1.10, 95%CI [1.01,1.20]) and GCS (OR 1.32, 95%CI [1.16,1.51]).
Conclusions
Early BRS was independently associated with short-term outcome after aSAH, regardless of beta-blockers or noradrenaline use. In the ‘clean data’ set, HR was significantly associated with outcome, whilst in the ‘noisy data’ set, BRS was significantly associated with outcome. A larger multicentre study is required to validate these findings.
{"title":"Can ‘noisy data’ perform as well as ‘clean data’ in outcome modeling after aneurysmal subarachnoid haemorrhage?","authors":"Agnieszka Uryga , Marek Czosnyka , Magdalena Kasprowicz , Małgorzata Burzyńska , Barbara Dragan , Karol Budohoski , Nathalie Nasr","doi":"10.1016/j.autneu.2025.103292","DOIUrl":"10.1016/j.autneu.2025.103292","url":null,"abstract":"<div><h3>Background</h3><div>Baroreflex sensitivity (BRS) is associated with clinical outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH); however few studies have investigated this in typical clinical settings. This two-centre study evaluated how outcome models differ when excluding patients who received beta-blockers and/or noradrenaline (‘clean data’ set) versus including all of them (‘noisy data’ set).</div></div><div><h3>Methods</h3><div>This retrospective study included consecutive aSAH patients from Addenbrooke's Hospital (UK) and Wroclaw Medical University (Poland). Early BRS was measured using the cross-correlation method. A favorable outcome was defined as a Glasgow Outcome Scale (GOS) score of 4–5 at discharge.</div></div><div><h3>Results</h3><div>A total of 108 patients were included, with 40 receiving beta-blockers and/or noradrenaline. The median age was 56 (IQR ± 17) years old, where 73 % were women. On admission, 57 % had a Glasgow Coma Scale (GCS) score of 13–15. Univariate logistic regression showed BRS was significantly associated with outcome in both the ‘clean data’ set (OR 1.16, 95%CI [1.02,1.30]) and ‘noisy data’ set (OR 1.10, 95%CI [1.03,1.18]). In multivariate analysis, the best ‘clean data’ model (χ<sup>2</sup> = 22.89, <em>p</em> < 0.001, AUC = 0.88) included heart rate (HR) (OR 0.93, 95%CI [0.87,0.99]) and GCS (OR 1.38, 95%CI [1.12,1.69]). The best ‘noisy data’ model (χ<sup>2</sup> = 32.27; <em>p</em> < 0.001, AUC = 0.84) included BRS (OR 1.10, 95%CI [1.01,1.20]) and GCS (OR 1.32, 95%CI [1.16,1.51]).</div></div><div><h3>Conclusions</h3><div>Early BRS was independently associated with short-term outcome after aSAH, regardless of beta-blockers or noradrenaline use. In the ‘clean data’ set, HR was significantly associated with outcome, whilst in the ‘noisy data’ set, BRS was significantly associated with outcome. A larger multicentre study is required to validate these findings.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103292"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-18DOI: 10.1016/j.autneu.2025.103315
Ayumi Fukazawa , Norio Hotta , Hoda Yeganehjoo , Amane Hori , Han-Kyul Kim , Gary A. Iwamoto , Scott A. Smith , Wanpen Vongpatanasin , Masaki Mizuno
Alzheimer's disease (AD) is the most common neurodegenerative disorder. It is characterized by synaptic loss and the increase of amyloid β (Aβ) in the brain often detrimentally affecting function. Brainstem is the key central integration site for sensory input from working skeletal muscle. Stimulation of skeletal muscle afferent fibers during muscle contraction increases blood pressure. However, whether AD alters or preserves the central processing of peripheral sensory afferent signals remains to be elucidated. Thus, we tested the hypothesis that the magnitude of the pressor response is functionally altered in intracerebroventricular-streptozotocin injected rats (ICV-STZ). Streptozotocin (3 mg/kg) was intracerebroventricularly injected into the lateral ventricle of male Sprague–Dawley rats. In parallel, a separate group of rats were treated with ICV saline as a vehicle control. Spatial learning and memory function were assessed using the Morris Water Maze behavioral test. Results demonstrate that ICV-STZ rats had a significantly longer time to reach a target platform compared to controls (P = 0.0046). ICV-STZ injection also significantly increased brainstem Aβ1–40 (P = 0.0082), but not Aβ1–42 (P = 0.0744). Further, the peak pressor and cardioaccelerator responses to tibial nerve stimulation were significantly attenuated in ICV-STZ rats compared to controls (ΔMAP: P = 0.0003, ΔHR: P = 0.0035). The findings suggest that the cardiovascular responses to electrical stimulation of sensory afferents are blunted in ICV-STZ rats.
阿尔茨海默病是最常见的神经退行性疾病。它的特点是突触丧失和大脑中β淀粉样蛋白（Aβ）的增加，往往对功能产生不利影响。脑干是骨骼肌感觉输入的关键中枢整合部位。肌肉收缩时对骨骼肌传入纤维的刺激使血压升高。然而，AD是否改变或保留了外周感觉传入信号的中央处理仍有待阐明。因此，我们验证了在脑室内注射链脲佐菌素的大鼠（ICV-STZ）中，升压反应的强度在功能上发生改变的假设。将链脲佐菌素（3 mg/kg）注入雄性sd大鼠侧脑室。同时，另一组大鼠用ICV生理盐水作为对照。采用Morris水迷宫行为测验评估空间学习和记忆功能。结果显示，ICV-STZ大鼠到达目标平台的时间明显长于对照组（P = 0.0046）。注射ICV-STZ能显著提高脑干Aβ1-40 (P = 0.0082)，但不能显著提高Aβ1-42 （P = 0.0744）。此外，与对照组相比，ICV-STZ大鼠对胫骨神经刺激的峰值加压和加速反应显著减弱（ΔMAP: P = 0.0003， ΔHR: P = 0.0035）。结果表明，ICV-STZ大鼠对感觉传入电刺激的心血管反应减弱。
{"title":"Blunted pressor response to peripheral sensory afferent nerve stimulation in intracerebroventricular-streptozotocin injected rats","authors":"Ayumi Fukazawa , Norio Hotta , Hoda Yeganehjoo , Amane Hori , Han-Kyul Kim , Gary A. Iwamoto , Scott A. Smith , Wanpen Vongpatanasin , Masaki Mizuno","doi":"10.1016/j.autneu.2025.103315","DOIUrl":"10.1016/j.autneu.2025.103315","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most common neurodegenerative disorder. It is characterized by synaptic loss and the increase of amyloid β (Aβ) in the brain often detrimentally affecting function. Brainstem is the key central integration site for sensory input from working skeletal muscle. Stimulation of skeletal muscle afferent fibers during muscle contraction increases blood pressure. However, whether AD alters or preserves the central processing of peripheral sensory afferent signals remains to be elucidated. Thus, we tested the hypothesis that the magnitude of the pressor response is functionally altered in intracerebroventricular-streptozotocin injected rats (ICV-STZ). Streptozotocin (3 mg/kg) was intracerebroventricularly injected into the lateral ventricle of male Sprague–Dawley rats. In parallel, a separate group of rats were treated with ICV saline as a vehicle control. Spatial learning and memory function were assessed using the Morris Water Maze behavioral test. Results demonstrate that ICV-STZ rats had a significantly longer time to reach a target platform compared to controls (<em>P =</em> 0.0046). ICV-STZ injection also significantly increased brainstem Aβ1–40 (<em>P =</em> 0.0082), but not Aβ1–42 (<em>P =</em> 0.0744). Further, the peak pressor and cardioaccelerator responses to tibial nerve stimulation were significantly attenuated in ICV-STZ rats compared to controls (ΔMAP: <em>P =</em> 0.0003, ΔHR: <em>P =</em> 0.0035). The findings suggest that the cardiovascular responses to electrical stimulation of sensory afferents are blunted in ICV-STZ rats.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103315"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicotine, a widely used toxic substance, has various receptors scattered throughout the body that have shown opposite effects on inflammatory disorders. However, the effects of nicotine on heart rate variability in ulcerative colitis are unclear. Therefore, the present study aimed to determine the effect of acute nicotine injection on heart rate variability in a rat model of ulcerative colitis.
Methods
Six male Wistar rat groups, containing vehicle, UC (induction of ulcerative colitis without treatment), and nicotine (0.5, 1, 1.5, and 2 mg/kg), were assessed. First, the rats were anesthetized and the initial electrocardiogram was recorded. Twenty-four hours after the induction of ulcerative colitis with 4 % acetic acid by rectal injection, a second electrocardiogram was recorded. Finally, 15 min after nicotine injection in each group, the last electrocardiogram was recorded. Linear and nonlinear indices of heart rate variability were extracted from the recorded R-R intervals.
Results
A single injection of nicotine at high doses increased the standard deviation of R-R intervals, root mean square of successive differences between normal heartbeats, ratio of the short-term deviation to the long-term deviation of R-R intervals, and entropy of R-R intervals in ulcerative colitis animals (at least P < 0.05).
Conclusions
Acute injection of nicotine at doses 1.5 and 2 mg/kg can improve R-R interval linear indices, balance the ratio of short-term deviation to long-term deviation, and modify the entropy in the induced ulcerative colitis rats. However, further research is needed for the clinical use of acute nicotine injection in ulcerative colitis.
{"title":"A single dose of nicotine modulates heart rate variability in rats with induced-ulcerative colitis","authors":"Diba Sadat Miraghaee , Azadeh Khalili , Gholamreza Bayat , Zahra Mousavi , Milad Nazari , Marjan Hosseini , Mahdi Goudarzvand , Roham Mazloom","doi":"10.1016/j.autneu.2025.103282","DOIUrl":"10.1016/j.autneu.2025.103282","url":null,"abstract":"<div><h3>Background and aims</h3><div>Nicotine, a widely used toxic substance, has various receptors scattered throughout the body that have shown opposite effects on inflammatory disorders. However, the effects of nicotine on heart rate variability in ulcerative colitis are unclear. Therefore, the present study aimed to determine the effect of acute nicotine injection on heart rate variability in a rat model of ulcerative colitis.</div></div><div><h3>Methods</h3><div>Six male Wistar rat groups, containing vehicle, UC (induction of ulcerative colitis without treatment), and nicotine (0.5, 1, 1.5, and 2 mg/kg), were assessed. First, the rats were anesthetized and the initial electrocardiogram was recorded. Twenty-four hours after the induction of ulcerative colitis with 4 % acetic acid by rectal injection, a second electrocardiogram was recorded. Finally, 15 min after nicotine injection in each group, the last electrocardiogram was recorded. Linear and nonlinear indices of heart rate variability were extracted from the recorded R-R intervals.</div></div><div><h3>Results</h3><div>A single injection of nicotine at high doses increased the standard deviation of R-R intervals, root mean square of successive differences between normal heartbeats, ratio of the short-term deviation to the long-term deviation of R-R intervals, and entropy of R-R intervals in ulcerative colitis animals (at least P < 0.05).</div></div><div><h3>Conclusions</h3><div>Acute injection of nicotine at doses 1.5 and 2 mg/kg can improve R-R interval linear indices, balance the ratio of short-term deviation to long-term deviation, and modify the entropy in the induced ulcerative colitis rats. However, further research is needed for the clinical use of acute nicotine injection in ulcerative colitis.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103282"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-29DOI: 10.1016/j.autneu.2025.103306
Dilara Kersebaum , Ralf Baron , Janne Gierthmühlen , Julia Forstenpointner
Hypermobile EDS (hEDS) is associated with joint hypermobility, early-onset osteoarthritis, chronic pain, and dysautonomia. This study explored sensory-vascular profiles, as both nociceptive and autonomic nerve fibers are part of the small-fiber group. The aim was to examine sensory-vascular characteristics in an hEDS family, with and without dysautonomia.
Five female participants (ages 12–60) underwent tilt-table testing, heart-rate-variability analysis, cutaneous vasoconstriction testing, thermal sensory- and microcirculation testing. Four reported pain; two had dysautonomia and vascular hyperelasticity. All exhibited A-delta fiber loss, while those with dysautonomia also showed C-fiber impairment.
Findings indicate dysautonomia and vascular maladaptation worsens with small-fiber dysfunction in hEDS.
{"title":"Autonomic and sensory dysfunction in hypermobile Ehlers-Danlos syndrome: How do small fibers contribute?","authors":"Dilara Kersebaum , Ralf Baron , Janne Gierthmühlen , Julia Forstenpointner","doi":"10.1016/j.autneu.2025.103306","DOIUrl":"10.1016/j.autneu.2025.103306","url":null,"abstract":"<div><div>Hypermobile EDS (hEDS) is associated with joint hypermobility, early-onset osteoarthritis, chronic pain, and dysautonomia. This study explored sensory-vascular profiles, as both nociceptive and autonomic nerve fibers are part of the small-fiber group. The aim was to examine sensory-vascular characteristics in an hEDS family, with and without dysautonomia.</div><div>Five female participants (ages 12–60) underwent tilt-table testing, heart-rate-variability analysis, cutaneous vasoconstriction testing, thermal sensory- and microcirculation testing. Four reported pain; two had dysautonomia and vascular hyperelasticity. All exhibited A-delta fiber loss, while those with dysautonomia also showed C-fiber impairment.</div><div>Findings indicate dysautonomia and vascular maladaptation worsens with small-fiber dysfunction in hEDS.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103306"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-04-19DOI: 10.1016/j.autneu.2025.103281
Jaiden Uppal, Jacquie R. Baker, Rashmin Hira, Kavithra Karalasingham, Shaun Ranada, Paras Deol, Robert S. Sheldon, Satish R. Raj
Head-up tilt (HUT) and active stand tests (AST) are used in the diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), but their relative diagnostic accuracy is unclear. This necessitates a direct comparison under standardized conditions. We aimed to compare the hemodynamic responses and diagnostic accuracy of AST vs. HUT in POTS.
To address this, patients with POTS (n = 60) completed a 10-min AST followed by HUT on the same day. Beat-to-beat hemodynamics were recorded during 10-min supine baselines and each test. Delta values were calculated for each test (upright 1-min averages minus baseline average).
Δ[heart rate] increased significantly over time (1_Min: 28 bpm to 10_Min: 40 bpm; PTime < 0.001), and was greater for HUT (33 bpm vs. 37 bpm; PASTvHUT = 0.01), with significant Time x Condition interaction (38 bpm vs. 42 bpm at10min; PINT < 0.001). Δ[stroke volume] declined over time (1_Min: -18 ml to 10_Min: -32 ml); PTime < 0.001), with no significant test or interaction effects (PASTvHUT = 0.36; PINT = 0.21). Δ[SBP] decreased (1_Min: −0.3 mmHg to 10_Min: −5.7 mmHg); PTime < 0.001) over time, with no test or interaction effects.
Fewer patients met POTS heart rate criteria during the AST (AST: 74 % vs. HUT: 98 %; p < 0.001). Lowering the threshold to 27 bpm for AST narrowed the gap but was still significantly higher for HUT (AST: 83 % vs HUT: 98 %; p = 0.02).
Orthostatic tachycardia differs between AST and HUT in patients with POTS. The proportion of patients with POTS meeting the heart rate diagnostic criteria differs significantly between AST and HUT, a discrepancy that can be mitigated by lowering the heart rate threshold for the AST.
{"title":"Physiological and clinical comparison of active stand and head-up tilt tests in Postural Orthostatic Tachycardia Syndrome (POTS)","authors":"Jaiden Uppal, Jacquie R. Baker, Rashmin Hira, Kavithra Karalasingham, Shaun Ranada, Paras Deol, Robert S. Sheldon, Satish R. Raj","doi":"10.1016/j.autneu.2025.103281","DOIUrl":"10.1016/j.autneu.2025.103281","url":null,"abstract":"<div><div>Head-up tilt (HUT) and active stand tests (AST) are used in the diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), but their relative diagnostic accuracy is unclear. This necessitates a direct comparison under standardized conditions. We aimed to compare the hemodynamic responses and diagnostic accuracy of AST vs. HUT in POTS.</div><div>To address this, patients with POTS (<em>n</em> = 60) completed a 10-min AST followed by HUT on the same day. Beat-to-beat hemodynamics were recorded during 10-min supine baselines and each test. Delta values were calculated for each test (upright 1-min averages minus baseline average).</div><div>Δ[heart rate] increased significantly over time (1_Min: 28 bpm to 10_Min: 40 bpm; P<sub>Time</sub> < 0.001), and was greater for HUT (33 bpm vs. 37 bpm; P<sub>ASTvHUT</sub> = 0.01), with significant Time x Condition interaction (38 bpm vs. 42 bpm at10min; P<sub>INT</sub> < 0.001). Δ[stroke volume] declined over time (1_Min: -18 ml to 10_Min: -32 ml); P<sub>Time</sub> < 0.001), with no significant test or interaction effects (P<sub>ASTvHUT</sub> = 0.36; P<sub>INT</sub> = 0.21). Δ[SBP] decreased (1_Min: −0.3 mmHg to 10_Min: −5.7 mmHg); P<sub>Time</sub> < 0.001) over time, with no test or interaction effects.</div><div>Fewer patients met POTS heart rate criteria during the AST (AST: 74 % vs. HUT: 98 %; <em>p</em> < 0.001). Lowering the threshold to 27 bpm for AST narrowed the gap but was still significantly higher for HUT (AST: 83 % vs HUT: 98 %; <em>p</em> = 0.02).</div><div>Orthostatic tachycardia differs between AST and HUT in patients with POTS. The proportion of patients with POTS meeting the heart rate diagnostic criteria differs significantly between AST and HUT, a discrepancy that can be mitigated by lowering the heart rate threshold for the AST.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103281"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-17DOI: 10.1016/j.autneu.2025.103311
Jeann L. Sabino-Carvalho , Rosa V. Guerrero , André L. Teixeira , Pedro R.P. Brandão , Lauro C. Vianna
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by non-motor symptoms and marked altered sympathetic and parasympathetic activity. However, it is currently unclear if inappropriate autonomic adjustments are manifested during rapid parasympathetic adjustments that occur following cessation of exercise and at the onset of isolated post-exercise ischemia (PEI). Herein, we tested the hypothesis that, compared to older and young men, PD patients would show attenuated heart rate (HR) recovery at exercise cessation due to impaired cardiac vagal reactivation. Eleven PD patients (66 ± 9 yr), 9 age-matched controls (64 ± 7 yr), and 10 young controls (21 ± 1 yr) were studied. All participants performed 90-s of isometric handgrip at 40 % of maximal voluntary contraction, followed by 3-min of PEI. HR (electrocardiography) was continuously recorded. HR recovery was defined as the difference between HR at the end of the exercise and at the end of the first 30-s of PEI. HR variability (HRV) during the first 30-s of recovery was quantified. Following the cessation of exercise, the HR recovery was significantly lower in PD and age-matched controls compared to young controls (Δ-10 ± 5 vs. Δ-14 ± 6 vs. Δ-26 ± 8 beats.min − 1 at 30s; P < 0.001; respectively). compared to controls. HRV increased less post-exercise in PD and age-matched controls compared to young controls. In summary, PD patients and age-matched controls demonstrate blunted parasympathetic reactivation. However, contrary to our hypothesis, PD patients did not exhibit further attenuation in HR recovery compared to age-matched controls, suggesting that PD does not exacerbate vagal reactivation impairments beyond those associated with aging.
帕金森病（PD）是一种常见的神经退行性疾病，以非运动症状和显著的交感和副交感神经活动改变为特征。然而，目前尚不清楚的是，在运动停止后和孤立性运动后缺血（PEI）发生时，不适当的自主神经调节是否在快速副交感神经调节中表现出来。在此，我们验证了这样一个假设，即与老年和年轻男性相比，PD患者在运动停止时由于心脏迷走神经再激活受损而表现出心率（HR）恢复减慢。研究对象为11例PD患者（66±9岁），9例年龄匹配的对照组（64±7岁）和10例年轻对照组（21±1岁）。所有参与者在40%的最大自主收缩时进行90秒的等距握力，然后进行3分钟的PEI。连续记录HR（心电图）。HR恢复被定义为运动结束时与PEI前30秒结束时HR的差异。对恢复后30秒内的心率变异性（HRV）进行量化。停止运动后，PD组和年龄匹配组的心率恢复明显低于年轻组（Δ-10±5 vs. Δ-14±6 vs. Δ-26±8）。Min−1,30s；P & lt;0.001;分别)。与对照组相比。与年轻对照组相比，帕金森病患者和年龄匹配的对照组运动后HRV增加较少。总之，PD患者和年龄匹配的对照组表现出迟钝的副交感神经再激活。然而，与我们的假设相反，与年龄匹配的对照组相比，PD患者在HR恢复方面没有表现出进一步的衰减，这表明PD不会加剧迷走神经再激活损伤，而不仅仅是与衰老相关的损伤。
{"title":"Cardiac vagal reactivation at the onset of muscle Metaboreflex activation is not further impaired in patients with Parkinson's disease","authors":"Jeann L. Sabino-Carvalho , Rosa V. Guerrero , André L. Teixeira , Pedro R.P. Brandão , Lauro C. Vianna","doi":"10.1016/j.autneu.2025.103311","DOIUrl":"10.1016/j.autneu.2025.103311","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a common neurodegenerative disorder characterized by non-motor symptoms and marked altered sympathetic and parasympathetic activity. However, it is currently unclear if inappropriate autonomic adjustments are manifested during rapid parasympathetic adjustments that occur following cessation of exercise and at the onset of isolated post-exercise ischemia (PEI). Herein, we tested the hypothesis that, compared to older and young men, PD patients would show attenuated heart rate (HR) recovery at exercise cessation due to impaired cardiac vagal reactivation. Eleven PD patients (66 ± 9 yr), 9 age-matched controls (64 ± 7 yr), and 10 young controls (21 ± 1 yr) were studied. All participants performed 90-s of isometric handgrip at 40 % of maximal voluntary contraction, followed by 3-min of PEI. HR (electrocardiography) was continuously recorded. HR recovery was defined as the difference between HR at the end of the exercise and at the end of the first 30-s of PEI. HR variability (HRV) during the first 30-s of recovery was quantified. Following the cessation of exercise, the HR recovery was significantly lower in PD and age-matched controls compared to young controls (Δ-10 ± 5 vs. Δ-14 ± 6 vs. Δ-26 ± 8 beats.min − 1 at 30s; <em>P</em> < 0.001; respectively). compared to controls. HRV increased less post-exercise in PD and age-matched controls compared to young controls. In summary, PD patients and age-matched controls demonstrate blunted parasympathetic reactivation. However, contrary to our hypothesis, PD patients did not exhibit further attenuation in HR recovery compared to age-matched controls, suggesting that PD does not exacerbate vagal reactivation impairments beyond those associated with aging.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103311"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-03-29DOI: 10.1016/j.autneu.2025.103274
John D. Akins, Takuro Washio, Qi Fu
Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.
{"title":"Autonomic control of blood pressure in women: The roles of hypertension and aging","authors":"John D. Akins, Takuro Washio, Qi Fu","doi":"10.1016/j.autneu.2025.103274","DOIUrl":"10.1016/j.autneu.2025.103274","url":null,"abstract":"<div><div>Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103274"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-17DOI: 10.1016/j.autneu.2025.103312
Ítalo C. Raulino , Vinícius H. Ferreira , Juliana R. Souza , Mauro de Oliveira , Daniela Accorsi-Mendonça , Julian F.R. Paton , Benedito H. Machado
We hypothetized that spontaneously hypertensive rats (SHRs) exposed to chronic intermittent hyperoxia should reduce the high baseline arterial pressure (hypertension) observed in these animals. The rational for this study was based-upon the known overactivity of carotid chemoreceptors in SHR and their significant contribution to the maintenance of an increased sympathetic outflow and hypertension. To test this hypothesis, we exposed SHR and Wistar Kyoto rats (WKY, control) to intermittent hyperoxia (IH, FIO2 increase from 20.8 to 30 % in 6 cycles/h) 8 h a day during 10 days. Systolic arterial pressure was evaluated every 2 days by tail plethysmography. At the end of the protocols the rats were anesthetized and catheters implanted for arterial pressure recordings and drug injections 24 hs later in the conscious freely moving condition. Respiratory frequency was evaluated by whole body plethysmography before and after the IH protocol and the cardiovascular and respiratory responses to peripheral chemoreflex activation (KCN) were evaluated one day after the end of protocol. Arterial blood samples were collected one day after the end of protocols for gas evaluation. The data shows that IH produced no significant change in mean arterial pressure of SHR [159 ± 9.02 (N = 4) vs 153 ± 7.85 mmHg (N = 7)] or WKY [115 ± 6.08 (N = 5) vs 111 ± 7.66 (N = 6) mmHg)] relative to their respective normoxic control. Since IH produced no changes in the cardiovascular parameters we propose that IH treatment protocol was not effective in reducing the overactivity of glomus cells in the carotid body of SHR.
{"title":"Chronic hyperoxic deactivation of peripheral chemoreceptors in spontaneously hypertensive rats: Does it lower arterial pressure?","authors":"Ítalo C. Raulino , Vinícius H. Ferreira , Juliana R. Souza , Mauro de Oliveira , Daniela Accorsi-Mendonça , Julian F.R. Paton , Benedito H. Machado","doi":"10.1016/j.autneu.2025.103312","DOIUrl":"10.1016/j.autneu.2025.103312","url":null,"abstract":"<div><div>We hypothetized that spontaneously hypertensive rats (SHRs) exposed to chronic intermittent hyperoxia should reduce the high baseline arterial pressure (hypertension) observed in these animals. The rational for this study was based-upon the known overactivity of carotid chemoreceptors in SHR and their significant contribution to the maintenance of an increased sympathetic outflow and hypertension. To test this hypothesis, we exposed SHR and Wistar Kyoto rats (WKY, control) to intermittent hyperoxia (IH, FIO<sub>2</sub> increase from 20.8 to 30 % in 6 cycles/h) 8 h a day during 10 days. Systolic arterial pressure was evaluated every 2 days by tail plethysmography. At the end of the protocols the rats were anesthetized and catheters implanted for arterial pressure recordings and drug injections 24 hs later in the conscious freely moving condition. Respiratory frequency was evaluated by whole body plethysmography before and after the IH protocol and the cardiovascular and respiratory responses to peripheral chemoreflex activation (KCN) were evaluated one day after the end of protocol. Arterial blood samples were collected one day after the end of protocols for gas evaluation. The data shows that IH produced no significant change in mean arterial pressure of SHR [159 ± 9.02 (<em>N</em> = 4) vs 153 ± 7.85 mmHg (<em>N</em> = 7)] or WKY [115 ± 6.08 (<em>N</em> = 5) vs 111 ± 7.66 (<em>N</em> = 6) mmHg)] relative to their respective normoxic control. Since IH produced no changes in the cardiovascular parameters we propose that IH treatment protocol was not effective in reducing the overactivity of glomus cells in the carotid body of SHR.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103312"},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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