Autonomic Neuroscience-Basic & Clinical最新文献_第10页

Functional knock out of Acid Sensing Ion Channel 3 prevents the exaggerated exercise pressor reflex in rats exercising on a treadmill 酸感应离子通道3的功能性敲除可防止大鼠在跑步机上运动时过度的运动压力反射

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-11 DOI: 10.1016/j.autneu.2025.103249

Gail D. Thomas , Shannon P. Higgins , Matthew J. Kuczmarski , Guillaume P. Ducrocq , Laura Anselmi , Victor Ruiz-Velasco , Marc P. Kaufman

We have compared the cardiovascular responses to treadmill exercise between wild-type (WT) Wistar Kyoto rats with their ASIC3 knock out (KO) counterparts both before and after their femoral arteries were bilaterally ligated. The rats were instrumented with radiotelemetry devices to measure arterial blood pressure and ran at a treadmill speed of 15–20 m/min. We found no difference in the pressor and cardioaccelerator responses to exercise between the WT and the ASIC3 KO rats when their femoral arteries were freely perfused. In contrast, the WT rats, but not the ASIC3 KO rats, displayed significantly larger peak and integrated pressor responses to treadmill exercise after both femoral arteries were ligated for 3 days. We also examined the effect of bilaterally injecting APETx2 into the substance of the gastrocnemius muscles on the cardiovascular responses to treadmill exercise in both the WT and the ASIC3 KO rats. We found that APETx2, an ASIC3 antagonist, attenuated the integrated pressor responses to exercise in the WT rats, after but not before the femoral arteries were ligated. Injection of APETx2 into the gastrocnemius muscles had no effect on the responses to exercise in the ASIC3 KO rats regardless of whether their femoral arteries were freely perfused or ligated. Our findings in conscious rats exercising on a treadmill extend our previous findings in reduced preparations in which we reported that ASIC3 “receptors” presumably on the intramuscular endings of group IV afferents play an important role in evoking the exaggerated component of the exercise pressor reflex induced by ischemia.

我们比较了野生型（WT） Wistar Kyoto大鼠与ASIC3敲除（KO）大鼠在双侧股动脉结扎前后对跑步机运动的心血管反应。用无线电遥测装置测量大鼠的动脉血压，并在跑步机上以15-20米/分钟的速度跑步。我们发现，当股动脉自由灌注时，WT和ASIC3 KO大鼠对运动的升压和加速反应没有差异。相比之下，在将两条股动脉结扎3天后，WT大鼠（而非ASIC3 KO大鼠）在跑步机运动中表现出更大的峰值和综合升压反应。我们还研究了在WT和ASIC3 KO大鼠中双侧向腓肠肌物质中注射APETx2对跑步机运动后心血管反应的影响。我们发现APETx2，一种ASIC3拮抗剂，在股动脉结扎之后而不是之前减弱了WT大鼠对运动的综合升压反应。无论股动脉是自由灌注还是结扎，在ASIC3 KO大鼠的腓肠肌中注射APETx2对运动反应没有影响。我们在跑步机上运动的有意识大鼠的研究结果扩展了我们之前在减少制剂中的发现，我们报道了ASIC3“受体”可能位于IV组传入神经的肌内末梢，在唤起由缺血引起的运动加压反射的夸大成分中起重要作用。

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引用次数: 0

Quantitative serum proteomic analysis for biomarker discovery in post-COVID-19 postural orthostatic tachycardia syndrome (PC-POTS) patients covid -19后体位性站立性心动过速综合征（PC-POTS）患者血清定量蛋白质组学分析发现生物标志物

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-08 DOI: 10.1016/j.autneu.2025.103247

Taekyung Ryu , Brittany L. Adler , Seeun Judy Jeong , David C. Lee , Ahmet Hoke , Chan Hyun Na , Tae Chung

Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition that is characterized by an excessive increase in heart rate upon orthostatic challenge. Before the COVID-19 pandemic, POTS affected 0.5 % to 1 % of the U.S. population. Since the pandemic, the incidence has risen sharply, adding an estimated 6–7 million new cases in the U.S. Despite its importance, there is currently no reliable biomarker for POTS, leading to significant diagnostic delays. A major hurdle in identifying biomarkers is the heterogeneous nature of the syndrome. To address this, we focused on a homogeneous subgroup of post-COVID-19 POTS (PC-POTS) patients. We conducted quantitative proteomics on sera from 9 PC-POTS patients and 9 healthy controls, identifying 31 proteins with significantly different abundances in PC-POTS patients. Most elevated proteins were linked to actin filaments or immune functions/inflammation. Weighted Gene Co-Expression Network Analysis revealed module 7 (M7) correlated strongly with PC-POTS diagnosis and related traits. The key proteins in M7 included MTPN, TAGLN2, ADP-ribosylation factor 1, PDLIM1, PPIA, CNN2, LGALSL, TXN, TLN1, TUBA4A, IL4, TREML1, GP1BA, and, all highly correlated with these traits. Cell-type enrichment analysis revealed that M7 was highly associated with immune and neuronal cells. The main pathways identified in M7 included the integrin signaling pathway, blood coagulation, and glycolysis. These findings suggest that the key proteins in M7 could serve as biomarkers for PC-POTS. This study uses quantitative proteomics to identify potential biomarkers that differentiate PC-POTS patients from healthy controls, establishing a foundation for further research and validation.

体位性站立性心动过速综合征（POTS）是一种慢性衰弱性疾病，其特征是在站立性挑战时心率过度增加。在COVID-19大流行之前，POTS影响了0.5%至1%的美国人口。自大流行以来，发病率急剧上升，在美国估计增加了600万至700万新病例，尽管它很重要，但目前还没有可靠的生物标志物来诊断POTS，导致严重的诊断延误。识别生物标志物的一个主要障碍是该综合征的异质性。为了解决这个问题，我们重点研究了一组同质的covid -19后POTS （PC-POTS）患者。我们对9名PC-POTS患者和9名健康对照者的血清进行了定量蛋白质组学分析，鉴定出31种在PC-POTS患者中丰度显著不同的蛋白质。大多数升高的蛋白与肌动蛋白丝或免疫功能/炎症有关。加权基因共表达网络分析显示，模块7 （M7）与PC-POTS的诊断及相关性状密切相关。M7的关键蛋白包括MTPN、TAGLN2、adp -核糖基化因子1、PDLIM1、PPIA、CNN2、LGALSL、TXN、TLN1、TUBA4A、IL4、TREML1、GP1BA，均与这些性状高度相关。细胞型富集分析显示M7与免疫细胞和神经元细胞高度相关。在M7中发现的主要途径包括整合素信号通路、凝血和糖酵解。这些发现表明M7中的关键蛋白可以作为PC-POTS的生物标志物。本研究利用定量蛋白质组学技术鉴定PC-POTS患者与健康对照的潜在生物标志物，为进一步研究和验证奠定基础。

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引用次数: 0

Changes and prognostic significance of autonomic cardiac regulation during ageing 自律性心脏调节在衰老过程中的变化及其预后意义

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-23 DOI: 10.1016/j.autneu.2025.103255

Elisa Karhumaa, Antti Vuoti, Antti M. Kiviniemi, M. Juhani Junttila, Mikko P. Tulppo, Heikki V. Huikuri, Olavi H. Ukkola, Juha S. Perkiömäki

Background

Data on the changes of heart rate variability (HRV) and their prognostic significance during ageing are limited.

Methods

HRV analyzes were done from standardized 45-min ECG recordings, which consisted of 15 min recordings in lying down, sitting positions and during walking. We used time domain-, frequency domain- and non-linear methods to estimate HRV. The baseline ECG recordings were done in 1991–1993 (n = 783) and follow up recordings were done in 2013–2014 (n = 466). Endpoints were reviewed in 2021.

Results

During a mean follow-up of 22.1 ± 0.7 years, high-, low- and very-low-frequency powers (HF, LF, VLF), standard deviation of RR intervals (SDNN), the short-term fractal-like scaling exponent analyzed by the detrended fluctuation analysis (DFA1) and approximate entropy (ApEn) decreased statistically significantly (p-values from <0.05 to <0.001). Larger decrease of VLF(ln) and LF(ln) predicted total and cardiovascular (CV) mortality in the multivariate model (p-values from <0.05 to <0.001). Baseline natural logarithm of LF (LF(ln)) dichotomized and DFA1 had the strongest prognostic value on total and CV-mortality in multivariate analysis after adjustments with relevant clinical characteristics. Also, lower values of baseline ApEn retained their predictive power for total mortality and decreased ratio of LF to HF (LF/HF) for CV-mortality after adjustments.

Conclusions

Almost all the HRV parameters decreased during ageing. Larger decrease of VLF(ln) and LF(ln) predicted total and CV-mortality after adjustments indicating that larger attenuation in cardiac autonomic regulation during ageing yields prognostic information. Of the baseline HRV parameters LF(ln) dichotomized and DFA1 had the strongest prognostic value on total and CV-mortality.

随着年龄的增长，心率变异性（HRV）的变化及其预后意义的数据有限。方法采用标准化的45分钟心电图记录进行shrv分析，其中包括躺卧、坐位和行走时的15分钟记录。我们使用时域、频域和非线性方法来估计HRV。基线心电图记录于1991-1993年（n = 783），随访记录于2013-2014年（n = 466）。2021年对终点进行了审查。结果在平均22.1±0.7年的随访中，高、低、甚低频功率（HF、LF、VLF）、RR区间标准差（SDNN）、短期分形标度指数（DFA1）和近似熵（ApEn）均有统计学意义（p值从0.05 ~ 0.001）。在多变量模型中，VLF（ln）和LF（ln）的较大下降预测了总死亡率和心血管死亡率（CV）（p值从<；0.05到<；0.001）。在多因素分析中，经相关临床特征调整后，LF（ln）二分和DFA1的基线自然对数对总死亡率和cv死亡率的预测价值最强。此外，较低的基线ApEn值在调整后对总死亡率和降低的LF/HF比率（LF/HF）对cv死亡率的预测能力保持不变。结论随着年龄的增长，HRV参数几乎全部下降。调整后，VLF（ln）和LF（ln）的较大下降预测了总死亡率和cv死亡率，表明衰老过程中心脏自主调节的较大衰减提供了预后信息。在基线HRV参数中，LF（ln）二分化和DFA1对总死亡率和cv死亡率具有最强的预后价值。

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引用次数: 0

Monotherapy with tolterodine or mirabegron is insufficient for ameliorating cyclophosphamide-induced bladder overactivity in rats 托特罗定或mirabegron单药治疗不足以改善大鼠环磷酰胺诱导的膀胱过度活动

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI: 10.1016/j.autneu.2025.103253

Håvard Fjelltveit , Thomas Carlsson , Fernando Perez , Ozgu Aydogdu , Bhavik Patel , Michael Winder

Monotherapy continues to be the most common pharmacological treatment option for patients with overactive bladder (OAB), despite evidence indicating that it may have inferior efficacy compared to combination therapy. This seems to be especially true for patients with concomitant cystitis. The current study examined the effects of monotherapy with either the antimuscarinic tolterodine or the β3 agonist mirabegron on bladder overactivity induced by bladder inflammation. Further, the possible involvement of nitric oxide (NO) was studied. For this purpose, rats were pretreated with either drug for 10 days. Bladder inflammation was induced by intraperitoneal injection with cyclophosphamide, with saline serving as control. Micturition parameters were assessed in a metabolic cage. Meanwhile, urine samples were collected and further analysed for NO content. After 16 h, the animals were euthanized, and their bladders were excised and examined immunohistochemically for signs of inflammation. Cyclophosphamide treatment led to bladder overactivity and obvious signs of inflammation. Neither treatment with tolterodine nor mirabegron could significantly alleviate the induced overactivity or the observed inflammation. Further, while induction of inflammation led to a significant increase in NO production, neither drug seemed to act by further enhancing its production. On the contrary, treatment with either tolterodine or mirabegron significantly decreased NO production in cyclophosphamide treated rats. Considering previous findings showing significant improvement by combination therapy, the current study indirectly implies this as the superior treatment option. Further studies are needed to verify the involvement, or lack thereof, of NO in the mechanism of action of drugs used to treat OAB.

单药治疗仍然是膀胱过动症（OAB）患者最常见的药物治疗选择，尽管有证据表明，与联合治疗相比，单药治疗的疗效可能较差。对于伴有膀胱炎的患者尤其如此。目前的研究考察了抗毒蕈碱托特罗定或β3激动剂mirabegron单药治疗膀胱炎症引起的膀胱过度活动的效果。进一步研究了一氧化氮（NO）的可能参与。为此，大鼠分别用两种药物预处理10天。腹腔注射环磷酰胺诱导膀胱炎症，生理盐水作为对照组。在代谢笼中评估排尿参数。同时，收集尿液样本并进一步分析NO含量。16小时后，对动物实施安乐死，切除膀胱，免疫组织化学检查炎症迹象。环磷酰胺治疗导致膀胱过度活动和明显的炎症迹象。托特罗定和米拉贝隆治疗均不能明显减轻诱导的过度活动或观察到的炎症。此外，虽然炎症诱导导致NO的产生显著增加，但两种药物似乎都没有通过进一步提高其产生来起作用。相反，托特罗定或mirabegron均可显著降低环磷酰胺处理大鼠的NO生成。考虑到先前的研究结果显示联合治疗有显著改善，当前的研究间接表明联合治疗是更好的治疗选择。需要进一步的研究来证实一氧化氮是否参与治疗OAB的药物的作用机制。

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引用次数: 0

Inter-individual variability in muscle sympathetic nerve activity at rest and during exercise: Disconnection with blood pressure 休息和运动时肌肉交感神经活动的个体间变异性：与血压无关

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-12 DOI: 10.1016/j.autneu.2025.103250

André L. Teixeira, Philip J. Millar

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) have provided fundamental insight into sympathetic discharge patterns at rest and during exercise in health and disease. A key feature of MSNA recordings at rest is a large inter-individual variability, even among healthy adults. The physiological consequences of inter-individual variability in MSNA are commonly discussed as being associated with the regulation of resting blood pressure. However, available evidence from large cross-sectional analyses demonstrate a near absence of an association between resting MSNA and blood pressure. Less appreciated, MSNA also exhibits inter-individual variability in response to stress, such as exercise. Again, the consequences of variability in MSNA are unclear and can be dissociated from the blood pressure response, particularly at low-to-moderate intensity muscle contractions for short durations (≤2 min). In this brief review, we summarize several examples of how inter-individual variability in MSNA is unrelated to blood pressure control at rest and during exercise and discuss potential mechanisms responsible for this observation, and key methodological considerations for future study design and interpretation. Additionally, we highlight several unanswered questions that could pave the way for future investigations in the field.

肌交感神经活动（MSNA）的微神经图记录为健康和疾病中休息和运动时交感神经放电模式提供了基本的见解。静息状态下MSNA记录的一个关键特征是个体间差异很大，即使在健康成人中也是如此。个体间MSNA变异的生理后果通常被认为与静息血压的调节有关。然而，来自大型横断面分析的现有证据表明，静息MSNA与血压之间几乎没有关联。较少被重视的是，MSNA也表现出个体对压力（如运动）的反应差异。同样，MSNA变异性的后果尚不清楚，可以与血压反应分离，特别是在短时间（≤2分钟）的低至中等强度肌肉收缩时。在这篇简短的综述中，我们总结了几个例子，说明MSNA的个体间变异如何与休息和运动时的血压控制无关，并讨论了导致这一观察结果的潜在机制，以及未来研究设计和解释的关键方学考虑。此外，我们强调了几个未解决的问题，这些问题可能为未来在该领域的调查铺平道路。

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引用次数: 0

Abnormal cardiovascular control during exercise: Role of insulin resistance in the brain 运动中心血管控制异常：胰岛素抵抗在大脑中的作用。

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-01-19 DOI: 10.1016/j.autneu.2025.103239

Juan A. Estrada , Amane Hori , Ayumi Fukazawa , Rie Ishizawa , Norio Hotta , Han-Kyul Kim , Scott A. Smith , Masaki Mizuno

During exercise circulatory adjustments to meet oxygen demands are mediated by multiple autonomic mechanisms, the skeletal muscle exercise pressor reflex (EPR), the baroreflex (BR), and by feedforward signals from central command neurons in higher brain centers. Insulin resistance in peripheral tissues includes sensitization of skeletal muscle afferents by hyperinsulinemia which is in part responsible for the abnormally heightened EPR function observed in diabetic animal models and patients. However, the role of insulin signaling within the central nervous system (CNS) is receiving increased attention as a potential therapeutic intervention in diseases with underlying insulin resistance. This review will highlight recent advances in our understanding of how insulin resistance induces changes in central signaling. The alterations in central insulin signaling produce aberrant cardiovascular responses to exercise. In particular, we will discuss the role of insulin signaling within the medullary cardiovascular control nuclei. The nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) are key nuclei where insulin has been demonstrated to modulate cardiovascular reflexes. The first locus of integration for the EPR, BR and central command is the NTS which is high in neurons expressing insulin receptors (IRs). The IRs on these neurons are well positioned to modulate cardiovascular responses to exercise. Additionally, the differences in IR density and presence of receptor isoforms enable specificity and diversity of insulin actions within the CNS. Therefore, non-invasive delivery of insulin into the CNS may be an effective means of normalizing cardiovascular responses to exercise in patients with insulin resistance.

在运动过程中，为满足氧气需求而进行的循环调节是由多种自主神经机制介导的，包括骨骼肌运动加压反射（EPR）、压力反射（BR）以及来自高级脑中枢的中央指令神经元的前馈信号。外周组织的胰岛素抵抗包括高胰岛素血症对骨骼肌传入神经的敏化，这是糖尿病动物模型和患者中观察到的EPR功能异常升高的部分原因。然而，胰岛素信号在中枢神经系统（CNS）中的作用作为潜在的胰岛素抵抗疾病的治疗干预受到越来越多的关注。这篇综述将强调我们对胰岛素抵抗如何诱导中枢信号变化的理解的最新进展。中枢胰岛素信号的改变导致心血管对运动的异常反应。特别地，我们将讨论胰岛素信号在髓系心血管控制核中的作用。孤立束核（NTS）和延髓吻侧腹外侧核（RVLM）是胰岛素调节心血管反射的关键核。EPR、BR和中枢指令的第一个整合位点是NTS，它在表达胰岛素受体（IRs）的神经元中含量很高。这些神经元上的ir可以很好地调节心血管对运动的反应。此外，IR密度的差异和受体同种异构体的存在使得胰岛素在中枢神经系统内的作用具有特异性和多样性。因此，无创向中枢神经系统输送胰岛素可能是胰岛素抵抗患者运动后心血管反应正常化的有效手段。

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引用次数: 0

Diencephalic and brainstem circuit mechanisms underlying autonomic cardiovascular adjustments to exercise: Recent insights from rodent studies 间脑和脑干回路机制对运动的自主心血管调节：来自啮齿动物研究的最新见解

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-09 DOI: 10.1016/j.autneu.2025.103248

Satoshi Koba, Emi Narai

Autonomic cardiovascular adjustments to exercise, essential for meeting the increased metabolic demands of exercising skeletal muscle, are regulated by motor volition-driven neural activation, i.e., central command. The contribution of brain mechanisms to these adjustments has been suggested for more than a century, yet the functional brain architecture remains incompletely understood. This article discusses recent findings primarily obtained from rodent studies utilizing advanced experimental tools, particularly those enabled by genetic engineering, such as optogenetics and viral neural tracing, to elucidate the diencephalic and brainstem circuits responsible for autonomic cardiovascular adjustments during voluntary exercise. Particular attention is paid to the central neural pathways and specific neuronal populations involved in transmitting central command signals, that drive not only somatic muscular activity but also autonomic cardiovascular responses. The uncovered diencephalic and brainstem circuits are relevant to understanding the brain substrate of central command, which is essential for maintaining cellular homeostasis and enhancing physical performance. Future studies and potential subjects for further investigation to deepen our understanding of the brain mechanisms underlying autonomic cardiovascular regulation are also discussed.

自主心血管对运动的调节，对于满足骨骼肌运动增加的代谢需求是必不可少的，是由运动意志驱动的神经激活，即中央命令来调节的。大脑机制对这些调整的贡献已经提出了一个多世纪，但大脑的功能结构仍然不完全清楚。本文主要讨论了利用先进实验工具进行啮齿动物研究的最新发现，特别是那些通过基因工程（如光遗传学和病毒神经追踪）实现的发现，以阐明在自愿运动期间负责自主心血管调节的间脑和脑干回路。特别关注的是中枢神经通路和特定的神经元群参与传递中枢指令信号，不仅驱动体细胞肌肉活动，而且自主心血管反应。间脑和脑干回路的发现与理解中枢指令的脑基质有关，而中枢指令对于维持细胞稳态和提高身体机能至关重要。本文还讨论了未来的研究和进一步研究的潜在主题，以加深我们对自主心血管调节的大脑机制的理解。

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引用次数: 0

Cardiac Vagal Nerve Activity During Exercise: New insights and future directions 运动中的心脏迷走神经活动：新的见解和未来的方向

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-13 DOI: 10.1016/j.autneu.2025.103254

Julia Shanks, Rohit Ramchandra

A new paradigm is emerging in which cardiac vagal nerve activity is maintained and increases during exercise. This paradigm challenges decades of studies that have quoted a withdrawal of cardiac vagal activity during exercise. Here, we outline the existing evidence for increased cardiac vagal activity. We also explain why previous indirect methods used to measure vagal activity might have indirectly led to incorrect conclusions about the role of the cardiac vagus during exercise. We will review evidence that vagal control of the sinoatrial node and the ventricles differs and how vagal neurotransmitters other than acetylcholine may regulate cardiac function during exercise. We will also suggest future directions for research to uncover how the cardiac vagus influences cardiac function and the mechanisms behind the increase in cardiac vagal nerve activity during exercise.

一种新的模式正在形成，即心脏迷走神经的活动在运动过程中得以维持并增加。这一范式对数十年来关于运动时心脏迷走神经活动减弱的研究提出了挑战。在此，我们概述了心脏迷走神经活动增加的现有证据。我们还解释了为什么以前用于测量迷走神经活动的间接方法可能会间接导致关于运动时心脏迷走神经作用的错误结论。我们将回顾迷走神经对中房结和心室内控制不同的证据，以及乙酰胆碱以外的迷走神经递质如何在运动中调节心脏功能。我们还将提出未来的研究方向，以揭示心脏迷走神经如何影响心脏功能以及运动时心脏迷走神经活动增加背后的机制。

引用次数: 0

Hypertonic saline solution evokes cardiovascular recovery in hemorrhagic rats dependent on GABA A and β-adrenergic transmission in the subfornical organ 高渗盐水溶液通过GABA A和β-肾上腺素能在皮质下器官的传递诱导出血性大鼠的心血管恢复

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2025-02-15 DOI: 10.1016/j.autneu.2025.103252

Amanda Barbosa Coelho da Silva , Stefanne Madalena Marques , James O. Fajemiroye , Eduardo Colombari , Carlos Henrique Xavier , Marcos Luiz Ferreira-Neto , Lara Marques Naves , Gustavo Rodrigues Pedrino

Background

Studies have reported the use of a hypertonic saline solution (HSS) for the treatment of hypotensive hemorrhage (HH). Despite the established role of central mechanisms in the cardiovascular recovery induced by HSS during HH, the involvement of the Subfornical Organ (SFO) in these responses remains to be elucidated. The present study evaluated the role of SFO and adrenergic neurotransmission in the nucleus in the cardiovascular responses to HSS infusion in hemorrhagic rats.

Methods

Mean arterial pressure (MAP), heart rate (HR), and aortic vascular resistance (AVR) were recorded in Wistar rats. HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. Nanoinjections of saline (NaCl; 0.15 M; control group; n = 7), muscimol (4 mM; GABAergic agonist; muscimol group; n = 7), or propranolol (10 mM; non-selective β-adrenergic blocker; propranolol group; n = 7) in SFO were performed 10 min after the onset of blood withdrawal, followed by HSS infusion (NaCl; 3 M; 1.8 ml∙kg⁻¹) 20 min after the beginning of HH.

Results

Hypotension, bradycardia, and aortic vasoconstriction were observed in all groups During HH. Sodium overload reestablished MAP and HR while maintaining aortic vasoconstriction in the control group. Activation of GABA A receptors or β-adrenergic receptor blockade in the SFO prevents HSS-induced recovery of MAP and HR. In addition, maintenance of aortic vasoconstriction induced by HSS infusion was abolished by SFO inhibition.

Conclusions

The results suggest that the integrity of SFO neurons and β-adrenergic neurotransmission are essential for cardiovascular recovery promoted by sodium overload in hemorrhagic rats.

背景研究报道了使用高渗盐水（HSS）治疗低血压性出血（HH）。尽管中枢机制在 HSS 诱导的 HH 期间心血管恢复中的作用已经确立，但角膜下器官（SFO）在这些反应中的参与仍有待阐明。本研究评估了 SFO 和细胞核中的肾上腺素能神经传递在出血大鼠输注 HSS 的心血管反应中的作用。方法记录 Wistar 大鼠的平均动脉压（MAP）、心率（HR）和主动脉血管阻力（AVR）。通过抽血进行 HH，直到 MAP 达到 60 mmHg。抽血开始 10 分钟后，在 SFO 中注射生理盐水（NaCl；0.15 M；对照组；n = 7）、麝香草酚（4 mM；GABA 能激动剂；麝香草酚组；n = 7）或普萘洛尔（10 mM；非选择性 β 肾上腺素能阻断剂；普萘洛尔组；n = 7），然后输注 HSS（NaCl；3 M；1.结果在 HH 期间，所有组均观察到低血压、心动过缓和主动脉血管收缩。钠超载可恢复血压和心率，同时维持对照组的主动脉血管收缩。在 SFO 中激活 GABA A 受体或阻断 β 肾上腺素能受体可防止 HSS 诱导的 MAP 和 HR 恢复。结论结果表明，SFO 神经元和 β 肾上腺素能神经递质的完整性对出血大鼠钠超载引起的心血管恢复至关重要。

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引用次数: 0

Distribution and morphology of CGRP-IR axons in flat-mounts of whole male and female mouse atria CGRP-IR轴突在雄性和雌性小鼠全心房平突的分布和形态。

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical

Pub Date : 2025-04-01 Epub Date: 2024-11-29 DOI: 10.1016/j.autneu.2024.103221

Kohlton Bendowski, Yuanyuan Zhang, Ariege Bizanti, Duyen Nguyen, Adhithyaa Nair, Jichao Ma, Jin Chen, Zixi Jack Cheng

Due to a lack of anatomical studies utilizing female specimens, it is unclear how the nociceptive innervation of the mouse heart compares between sexes. To address this, flat-mount preparations of the left and right atria of male and female mice were immunohistochemically labeled for calcitonin gene-related peptide (CGRP, a common marker for nociceptive nerves), imaged, and digitally traced in high quality. The results show that 1) A network of CGRP-IR axons densely innervated the right and left atria. Large nerve bundle entry points and regional concentration of CGRP-IR axons were similar in both sexes. 2) The detailed distribution of CGRP-IR bundles and axons were digitized and mapped using Arivis (Zeiss) Vision4D software. The general distribution patterns in male and female mice were comparable to one another. 3) The density of CGRP-IR axons in the sinoatrial (SA) node region (Male: 0.0258 μm/μm² ± 0.003; Female: 0.0347 μm/μm² ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm² ± 0.001; Female: 0.0228 μm/μm² ± 0.005) were not found to be significantly different. 4) The distance between adjacent varicosities in the auricle (Male: 4.049 μm ± 0.3; Female: 4.241 μm ± 0.34), SA node region (Male: 2.812 μm ± 0.21; Female: 3.352 μm ± 0.29), and AV node region (Male: 2.999 μm ± 0.3; Female: 3.526 μm ± 0.26) were not significantly different between sexes. 5) Likewise, maximum varicosity diameters in the auricle (Male: 0.5356 μm ± 0.04; Female: 0.5274 μm ± 0.03), SA node region (Male: 0.4714 μm ± 0.02; Female: 0.5634 μm ± 0.04), and AV node region (Male: 0.5103 μm ± 0.02; Female: 0.5103 μm ± 0.03) between male and female specimens were similar. Our data shows the comparable nature of the CGRP-IR axons in mouse atria in both sexes. Moreover, this is the first time we employed flat-mount preparations of whole atria to analyze the distribution of CGRP-IR axons in male and female mice.

由于缺乏利用雌性标本的解剖学研究，目前尚不清楚小鼠心脏的伤害神经支配如何在性别之间进行比较。为了解决这一问题，将雌雄小鼠左右心房的平载制备物免疫组织化学标记为降钙素基因相关肽（CGRP，一种常见的伤害神经标记物），成像并进行高质量的数字追踪。结果表明：1)CGRP-IR轴突网络密集支配左右心房。大神经束入口点和CGRP-IR轴突的区域浓度在两性中相似。2)利用Arivis (Zeiss) Vision4D软件对CGRP-IR束和轴突的详细分布进行数字化绘制。雄性和雌性小鼠的总体分布模式彼此具有可比性。3)窦房结区CGRP-IR轴突密度(男性：0.0258 μm/μm2±0.003；女性：0.0347 μm/μm2±0.006)和房室（AV）结区(男性：0.0138 μm/μm2±0.001；女性：0.0228 μm/μm2±0.005)，差异无统计学意义。4)耳廓内相邻静脉曲张间距(男性：4.049 μm±0.3；女:4.241μm±0.34),SA节点区域(男:2.812μm±0.21;女性：3.352 μm±0.29)，房室结区(男性：2.999 μm±0.3；女性：3.526 μm±0.26)，性别间差异无统计学意义。5)同样，耳廓最大静脉曲张直径(男性：0.5356 μm±0.04；母端：0.5274 μm±0.03)，SA节点区域(公端：0.4714 μm±0.02；女性：0.5634 μm±0.04)，房室结区(男性：0.5103 μm±0.02；雌性：0.5103 μm±0.03)，雌雄相近。我们的数据显示了两性小鼠心房中CGRP-IR轴突的可比性。此外，这是我们第一次使用全心房平装制剂来分析雄性和雌性小鼠CGRP-IR轴突的分布。

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