Autonomic Neuroscience-Basic & Clinical最新文献

{"title":"Validation of symptom measures in patients under investigation for postural orthostatic tachycardia syndrome (POTS): The Orthostatic Grading Scale (OGS) and the Symptom Screen for Small-fiber Polyneuropathy (SSS)","authors":"Iris Knoop ,&nbsp;Annie S.K. Jones ,&nbsp;Nicholas Gall ,&nbsp;Joseph Chilcot ,&nbsp;William Pascoe ,&nbsp;Rona Moss-Morris","doi":"10.1016/j.autneu.2023.103130","DOIUrl":"https://doi.org/10.1016/j.autneu.2023.103130","url":null,"abstract":"<div><h3>Objectives</h3><p><span>Postural Orthostatic Tachycardia Syndrome<span> (POTS) presents with a range of poorly delineated symptoms across several domains. There is an urgent need for standardized symptom reporting in POTS, but a lack of validated symptom burden instruments. Our aim was to evaluate the psychometric<span> properties of two symptom burden measures: the Orthostatic Grading Scale (OGS) and the Symptom Screen for Small-Fiber Polyneuropathy (SSS), </span></span></span>in patients under investigation for suspected POTS.</p></div><div><h3>Design</h3><p>Psychometric validation study.</p></div><div><h3>Methods</h3><p>Confirmatory factor analysis (CFA) tested the factor structure of the SSS and OGS completed by 149 patients under investigation for POTS. Scale reliability and validity were assessed. The uni-dimensionality of the SSS was assessed through principal component analysis (PCA).</p></div><div><h3>Results</h3><p>CFA of the OGS revealed that a 1-factor structure had adequate fit. CFA of the SSS revealed that a 5-factor structure had generally appropriate fit supporting the originally proposed 5 factors (1: Gastrointestinal, 2: Somatosensory, 3: Miscellaneous, 4: Microvascular, and 5: Urological). In addition, the SSS demonstrated sufficient uni-dimensionality in the PCA, warranting use of a single total score. Omega coefficients of both measures indicated satisfactory internal reliability (0.668–0.931). Correlations with related constructs (distress (K10 score), <em>r</em> = 0.317–0.404, <em>p</em> &lt; 0.001) and heart rate indices (with the OGS, <em>r</em> = 0.211–0.294, <em>p</em> &lt; 0.05) suggested sound convergent and divergent validity.</p></div><div><h3>Conclusions</h3><p>Initial evidence suggests that the OGS and SSS have good psychometric properties for use in populations with suspected and confirmed POTS.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"250 ","pages":"Article 103130"},"PeriodicalIF":2.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134657302","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}

{"title":"Targeted stimulation of the vagus nerve reduces renal injury in female mice with systemic lupus erythematosus","authors":"Caroline Gusson Shimoura ,&nbsp;Cassandra Y. Stubbs ,&nbsp;Sarika Chaudhari ,&nbsp;Viet Q. Dinh ,&nbsp;Keisa W. Mathis","doi":"10.1016/j.autneu.2023.103129","DOIUrl":"10.1016/j.autneu.2023.103129","url":null,"abstract":"<div><p><span>Pharmacological stimulation<span><span> of the vagus nerve<span> has been shown to suppress inflammation and reduce blood pressure in a murine model of systemic lupus erythematosus (SLE) that is characterized by hypertension, inflammation, renal injury and </span></span>dysautonomia. The present study aims to directly stimulate vagal nerves at the level of the dorsal motor nucleus of the vagus (DMV) using designer receptors exclusively activated by designer drugs (DREADDs) to determine if there is similar protection and confirm mechanism. Female </span></span><em>NZBWF1/J</em> (SLE) mice and <em>NZW/LacJ</em> mice (controls, labeled as <em>NZW</em><span><span> throughout) received bilateral microinjections of pAAV-hSyn-hM3D(Gq)-mCherry or control </span>virus<span><span> into the DMV at 31 weeks of age. After two weeks of recovery and viral transfection, the DREADD agonist clozapine-N-oxide (CNO; 3 mg/kg) was injected subcutaneously for an additional 14 days. At 35 weeks, </span>mean arterial pressure (MAP; mmHg) was increased in SLE mice compared to </span></span><em>NZW</em><span><span> mice, but selective activation of DMV neurons did not significantly alter MAP in either group. SLE mice had higher indices of renal injury including albumin excretion rate (μg/day), glomerulosclerosis index, </span>interstitial fibrosis, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) compared to </span><em>NZW</em> mice. Selective DMV neuronal activation reduced albumin excretion rate, glomerulosclerosis, interstitial fibrosis, and NGAL in SLE mice but not <em>NZW</em> mice. Together, these data indicate that selective activation of neurons within the DMV by DREADD protects the kidney suggesting an important role of vagus-mediated pathways in the progression of renal injury in SLE.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"250 ","pages":"Article 103129"},"PeriodicalIF":2.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720668","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}

{"title":"Mechanosensitive channels in the mechanical component of the exercise pressor reflex","authors":"Amane Hori ,&nbsp;Ayumi Fukazawa ,&nbsp;Kimiaki Katanosaka ,&nbsp;Masaki Mizuno ,&nbsp;Norio Hotta","doi":"10.1016/j.autneu.2023.103128","DOIUrl":"10.1016/j.autneu.2023.103128","url":null,"abstract":"<div><p>The cardiovascular response is appropriately regulated during exercise to meet the metabolic demands of the active muscles. The exercise pressor reflex is a neural feedback mechanism through thin-fiber muscle afferents activated by mechanical and metabolic stimuli in the active skeletal muscles. The mechanical component of this reflex is referred to as skeletal muscle mechanoreflex. Its initial step requires mechanotransduction mediated by mechanosensors, which convert mechanical stimuli into biological signals. Recently, various mechanosensors have been identified, and their contributions to muscle mechanoreflex have been actively investigated. Nevertheless, the mechanosensitive channels responsible for this muscular reflex remain largely unknown. This review discusses progress in our understanding of muscle mechanoreflex under healthy conditions, focusing on mechanosensitive channels.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"250 ","pages":"Article 103128"},"PeriodicalIF":2.7,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489262","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}

{"title":"Distribution and morphology of calcitonin gene-related peptide (CGRP) innervation in flat mounts of whole rat atria and ventricles","authors":"Jin Chen ,&nbsp;Kohlton T. Bendowski ,&nbsp;Ariege Bizanti ,&nbsp;Yuanyuan Zhang ,&nbsp;Jichao Ma ,&nbsp;Donald B. Hoover ,&nbsp;David Gozal ,&nbsp;Kalyanam Shivkumar ,&nbsp;Zixi Jack Cheng","doi":"10.1016/j.autneu.2023.103127","DOIUrl":"10.1016/j.autneu.2023.103127","url":null,"abstract":"<div><p><span>Calcitonin gene-related peptide (CGRP) is widely used as a marker for nociceptive afferent axons. However, the distribution of CGRP-IR axons has not been fully determined in the whole rat heart. Immunohistochemically labeled flat-mounts of the right and left atria<span> and ventricles, and the interventricular septum (IVS) in rats for CGRP were assessed with a Zeiss imager to generate complete montages of the entire atria, ventricles, and septum, and a </span></span>confocal microscope<span><span> was used to acquire detailed images of selected regions. We found that 1) CGRP-IR axons extensively innervated all regions of the atrial walls including the sinoatrial node<span> region, auricles<span><span>, atrioventricular node region, superior/inferior vena cava, left pre-caval vein, and </span>pulmonary veins. 2) CGRP-IR axons formed varicose terminals around individual neurons in some cardiac </span></span></span>ganglia<span> but passed through other ganglia without making appositions with cardiac neurons. 3) Varicose CGRP-IR axons innervated the walls of blood vessels. 4) CGRP-IR axons extensively innervated the right/left ventricular walls and IVS. Our data shows the rather ubiquitous distribution of CGRP-IR axons in the whole rat heart at single-cell/axon/varicosity resolution for the first time. This study lays the foundation for future studies to quantify the differences in CGRP-IR axon innervation between sexes, disease models, and species.</span></span></p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"251 ","pages":"Article 103127"},"PeriodicalIF":2.7,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009792","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}

{"title":"Heart rate variability and cardiovascular risk factors in patients with rheumatoid arthritis: A longitudinal study","authors":"Sofia Erelund ,&nbsp;Anna Södergren ,&nbsp;Urban Wiklund ,&nbsp;Nina Sundström","doi":"10.1016/j.autneu.2023.103119","DOIUrl":"10.1016/j.autneu.2023.103119","url":null,"abstract":"<div><h3>Background</h3><p>It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time.</p></div><div><h3>Method</h3><p>HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60 years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed.</p></div><div><h3>Results</h3><p>At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11 years, but no significant association was found with baseline HRV data.</p></div><div><h3>Conclusion</h3><p>This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"249 ","pages":"Article 103119"},"PeriodicalIF":2.7,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579304","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}

{"title":"The clinical utility of the Breathing Pattern Assessment Tool (BPAT) to identify dysfunctional breathing (DB) in individuals living with postural orthostatic tachycardia syndrome (POTS)","authors":"Charles C. Reilly ,&nbsp;Sarah V. Floyd ,&nbsp;Shehnaz Raniwalla ,&nbsp;Nicholas Gall ,&nbsp;Gerrard F. Rafferty","doi":"10.1016/j.autneu.2023.103104","DOIUrl":"10.1016/j.autneu.2023.103104","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Dysfunctional breathing (DB) resulting in inappropriate breathlessness is common in individuals living with postural orthostatic tachycardia syndrome (POTS). DB in POTS is complex, multifactorial, and not routinely assessed clinically outside of specialist centres. To date DB in POTS has been identified and diagnosed predominately via cardiopulmonary exercise testing (CPEX), </span>hyperventilation provocation testing and/or specialist </span>respiratory physiotherapy assessment. The Breathing Pattern Assessment Tool (BPAT) is a clinically validated diagnostic tool for DB in Asthma. There are, however, no published data regarding the use of the BPAT in POTS. The aim of this study was therefore to assess the potential clinic utility of the BPAT in the diagnosis of DB in individuals with POTS.</p></div><div><h3>Methods</h3><p>A retrospective observational cohort study of individuals with POTS referred to respiratory physiotherapy for formal assessment of DB. DB was determined by specialist respiratory physiotherapist assessment which included physical assessment of chest wall movement/breathing pattern. The BPAT and Nijgmegen questionnaire were also completed. Receiver operating characteristics (ROC) analysis was used to compare the physiotherapy assessment based diagnosis of DB to the BPAT score.</p></div><div><h3>Results</h3><p>Seventy-seven individuals with POTS [mean (sd) age 32 (11) years, 71 (92 %) female] were assessed by a specialist respiratory physiotherapist, with 65 (84 %) being diagnosed with DB. Using the established BPAT cut off of four or more, receiver operating characteristics (ROC) analysis indicated a sensitivity of 87 % and specificity of 75 % for diagnosing DB in individuals with POTS with an area under the curve (AUC) of 0.901 (95 % CI 0.803–0.999), demonstrating excellent discriminatory ability.</p></div><div><h3>Conclusion</h3><p>BPAT has high sensitivity and moderate specificity for identifying DB in individuals living with POTS.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"248 ","pages":"Article 103104"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10330094","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}

{"title":"Aortic stiffness contributes to greater pressor responses during static hand grip exercise in healthy young and middle-aged normotensive men","authors":"Denis J. Wakeham ,&nbsp;Rachel N. Lord ,&nbsp;Jack S. Talbot ,&nbsp;Freya M. Lodge ,&nbsp;Bryony A. Curry ,&nbsp;Tony G. Dawkins ,&nbsp;Lydia L. Simpson ,&nbsp;Christopher J.A. Pugh ,&nbsp;Rob E. Shave ,&nbsp;Jonathan P. Moore","doi":"10.1016/j.autneu.2023.103106","DOIUrl":"10.1016/j.autneu.2023.103106","url":null,"abstract":"<div><p><span><span><span>Central arterial stiffness can influence exercise blood pressure (BP) by increasing the rise in </span>arterial pressure<span> per unit increase in aortic inflow. Whether central arterial stiffness influences the pressor response<span><span> to isometric handgrip exercise (HG) and post-exercise muscle ischemia (PEMI), two common laboratory tests to study sympathetic control of BP, is unknown. We studied 46 healthy non-hypertensive males (23 young and 23 middle-aged) during HG (which increases in cardiac output [Q̇c]) and isolated metaboreflex activation PEMI (no change or decreases in Q̇c). Aortic stiffness (aortic </span>pulse wave velocity<span> [aPWV]; applanation tonometry via SphygmoCor) was measured during supine rest and was correlated to the pressor responses to HG and PEMI. BP (photoplethysmography) and muscle sympathetic </span></span></span></span>nerve activity (MSNA) were continuously recorded at rest, during HG to fatigue (35 % maximal voluntary contraction) and 2-min of PEMI. aPWV was higher in middle-aged compared to young males (7.1 ± 0.9 vs 5.4 ± 0.7 m/s, </span><em>P</em><span> &lt; 0.001). Middle-aged males also exhibited greater increases in systolic pressure (∆30 ± 11 vs 10 ± 8 mmHg) and MSNA (∆2313 ± 2006 vs 1387 ± 1482 %/min) compared to young males during HG (both, </span><em>P</em> &lt; 0.03); with no difference in the Q̇c response (<em>P</em> = 0.090). Responses to PEMI were not different between groups. Sympathetic transduction during these stressors (MSNA-diastolic pressure slope) was not different between groups (<em>P</em> &gt; 0.341). Middle-aged males displayed a greater increase in SBP per unit change of Q̇c during HG (∆SBP/∆Q̇c; 21 ± 18 vs 6 ± 10 mmHg/L/min, <em>P</em> = 0.004), with a strong and moderate relationship between the change in systolic (<em>r</em> = 0.53, <em>P</em><span> &lt; 0.001) and diastolic pressure (</span><em>r</em> = 0.34, <em>P</em> = 0.023) and resting aPWV, respectively; with no correlation during PEMI. Central arterial stiffness can modulate pressor responses during stimuli associated with increases in cardiac output and sympathoexcitation in healthy males.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"248 ","pages":"Article 103106"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968054","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}

{"title":"Adrenal gland response to adrenocorticotropic hormone is intact in patients with postural orthostatic tachycardia syndrome","authors":"Jill K.H. Laurin ,&nbsp;Oyebimbola A. Oyewunmi ,&nbsp;Emily M. Garland ,&nbsp;Alfredo Gamboa ,&nbsp;Victor C. Nwazue ,&nbsp;Sachin Y. Paranjape ,&nbsp;Bonnie K. Black ,&nbsp;Luis E. Okamoto ,&nbsp;Cyndya A. Shibao ,&nbsp;Italo Biaggioni ,&nbsp;David Robertson ,&nbsp;André Diedrich ,&nbsp;William D. Dupont ,&nbsp;Robert S. Sheldon ,&nbsp;Satish R. Raj","doi":"10.1016/j.autneu.2023.103105","DOIUrl":"10.1016/j.autneu.2023.103105","url":null,"abstract":"<div><h3>Background</h3><p><span>Many patients with postural orthostatic tachycardia syndrome<span><span> (POTS) are hypovolemic with plasma volume deficits of 10–30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in </span>angiotensin II, pointing to potential </span></span>adrenal dysfunction<span><span><span>. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and </span>cortisol following </span>adrenocorticotropin hormone (ACTH) stimulation.</span></p></div><div><h3>Methods</h3><p>While on a low Na⁺ diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 μg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 μg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h.</p></div><div><h3>Results</h3><p>Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8–61.8 ng/dL] vs. 46.1 ng/dL [36.7–84.9 ng/dL]; <em>P</em> = 1.000) or maximally (56.4 ng/dL [49.2–67.1 ng/dL] vs. 49.5 ng/dL [39.1–82.8 ng/dL]; <em>P</em><span> = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 μg/dL [36.1–47.7 μg/dL] vs. 39.3 μg/dL [35.4–46.6 μg/dL]; </span><em>P</em> = 0.724) or maximally (39.9 μg/dL [33.9–45.4 μg/dL] vs. 42.0 μg/dL [37.6–49.7 μg/dL]; <em>P</em> = 0.354).</p></div><div><h3>Conclusions</h3><p><span>ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to </span>hormonal stimulation is intact in patients with POTS.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"248 ","pages":"Article 103105"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039049","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}

{"title":"Enhancement of muscarinic receptor–mediated excitation in spontaneously hypertensive rat adrenal medullary chromaffin cells","authors":"Masumi Inoue,&nbsp;Keita Harada","doi":"10.1016/j.autneu.2023.103108","DOIUrl":"10.1016/j.autneu.2023.103108","url":null,"abstract":"<div><p><span><span>One of the mechanisms for hypertension is an increase in blood catecholamines due to increased secretion from sympathetic nerve terminals and adrenal medullary chromaffin (AMC) cells. </span>Spontaneously hypertensive rats<span><span><span> (SHRs) are used as an animal model of hypertension. Catecholamine secretion in AMC cells occurs in response to </span>humoral factors<span> and neuronal inputs from the sympathetic nerve fibres. Acetylcholine (ACh) released from the nerve terminals activates nicotinic as well as </span></span>muscarinic ACh receptors<span>. The present experiment aimed to elucidate whether muscarinic receptor–mediated excitation is altered in SHR AMC cells and, if it is, how. Compared with normotensive rat AMC cells, muscarinic stimulation induced greater catecholamine secretion and larger depolarising inward currents in SHR AMC cells. In contrast to normotensive rat AMC cells, the muscarine-induced current consisted of quinine-sensitive and quinine-insensitive components. The former and the latter are possibly ascribed to nonselective cation channel activation and TWIK-related acid-sensitive K</span></span></span>⁺<span><span> (TASK) channel inhibition, as noted in guinea pig AMC cells. In fact, immunoreactive material for TASK1 and several isoforms of transient receptor potential canonical (TRPC) channels was detected in SHR AMC cells. Stromal interaction molecule 1 (STIM1), which plays an essential role for heteromeric TRPC1–TRPC4 channel formation and is not expressed in normotensive rat AMC cells, was detected in the cytoplasm and co-localised with </span>TRPC1. The expression of muscarinic M</span>₁ receptors was enhanced in SHR AMC cells compared with normotensive rats. The results indicate that muscarinic excitation is enhanced in SHR AMC cells, probably through facilitation of TRPC channel signalling.</p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"248 ","pages":"Article 103108"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9983254","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}

{"title":"Sympathetic and angiotensinergic activity in spontaneously hypertensive rats treated with 3-amino-1,2,4-triazole","authors":"Roberto Braz Pontes,&nbsp;Débora S.A. Colombari,&nbsp;Patrícia M. De Paula,&nbsp;Eduardo Colombari,&nbsp;Carina A.F. Andrade,&nbsp;Laurival A. De Luca Jr,&nbsp;José V. Menani","doi":"10.1016/j.autneu.2023.103107","DOIUrl":"10.1016/j.autneu.2023.103107","url":null,"abstract":"<div><p><span><span>Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or </span>spontaneously hypertensive rats (SHRs) is attenuated by increased central H</span>₂O₂ concentration, produced either by direct H₂O₂<span> icv injection or by increased endogenous H</span>₂O₂<span><span><span><span> centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on </span>arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280–330 g were used. </span>Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute </span>intravenous injection<span> of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment<span> with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium<span> (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (−25 ± 3, vs saline −38 ± 4 mmHg). Losartan (angiotensinergic AT</span></span></span></span>₁<span> receptor blocker) produced a significant depressor response 4 h after ATZ (−22 ± 4, vs. saline: −2 ± 4 mmHg) and in 3-day ATZ treated SHRs (−25 ± 5, vs. saline: −9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.</span></p></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"248 ","pages":"Article 103107"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357453","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}