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Temporal effects of inflammation on the autonomic control of circulation during exercise in type 2 diabetic rats

炎症对 2 型糖尿病大鼠运动过程中循环自主神经控制的时间影响

基本信息

批准号：
10715362
负责人：
Audrey J Stone
金额：
$ 7.93万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2024-12-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY/ABSTRACT A reflex arising from the contraction of hindlimb skeletal muscles is an important neural mechanism that is responsible for the cardiovascular adjustments to exercise. These adjustments, which include increases in peripheral vascular resistance, cardiac contractility and heart rate, function to increase arterial blood flow and oxygen to the exercising muscles, and in turn support their ability to contract. This neural mechanism has been named the exercise pressor reflex, and its afferent arm is comprised of group III and IV afferents whose endings are located in and near the muscle interstitium. Group III and IV afferents are commonly affected by diabetes which often results in peripheral neuropathy causing a range of problems from allodynia to hyperalgesia to hypoalgesia as the disease progresses. Chronic inflammation is one of the known mechanisms for peripheral neuropathy, directly affecting group III and IV afferents, and is present in diabetes, aging, and cardiovascular disease. The overall goal of the experiments proposed is to shed light on the role of pro-inflammatory cytokines on the exercise pressor reflex as diabetes progresses. In the proposed experiments, we will pay particular attention to two important pro-inflammatory cytokines known to be upregulated in diabetics and those with cardiovascular disease, namely interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). We will also pay particular attention to two important anti-inflammatory cytokines known to be downregulated in diabetics and those with cardiovascular disease, namely interleukin 10 (IL-10), and interleukin 4 (IL-4).We will examine in decerebrated, unanesthetized rats the pressor, cardioaccelerator, and sympathetic activity responses to static and intermittent contraction both before and during pharmacological blockade of the cytokine receptors. The proposed experiments will also quantify the potential up-regulation or down-regulation of these circulating cytokines using serum samples in multiplex assays. We anticipate that these experiments will provide new information about the role of pro- and anti-inflammatory cytokines in the progression of diabetes on the autonomic control of circulation during exercise. ***There is no change in the scope for this supplement.

项目摘要/摘要后肢骨骼肌收缩产生的反射是一种重要的神经机制，即负责心血管调节运动。这些调整，包括增加外周血管阻力，心脏收缩能力和心率，增加动脉血流量和氧气供应给运动肌肉，进而支持他们收缩的能力。这种神经机制一直是名为运动加压反射，其传入臂由III和IV类传入组成，它们的末梢位于肌肉间质及其附近。第三类和第四类传入神经通常受糖尿病的影响这通常会导致周围神经病变，导致一系列问题，从痛觉过敏到痛觉过敏，再到随着疾病的发展而出现痛觉减退。慢性炎症是外周血肿的已知机制之一神经病变，直接影响III和IV组传入，并存在于糖尿病、衰老和心血管疾病中疾病。这些实验的总体目标是阐明促炎细胞因子的作用。糖尿病进展过程中的运动升压反射。在拟议的实验中，我们将特别支付注意两种重要的促炎细胞因子在糖尿病患者和慢性阻塞性肺疾病患者中上调心血管疾病，即白介素1β(IL-1β)和白介素6(IL-6)。我们还将特别支付注意两种重要的抗炎细胞因子，已知在糖尿病患者和糖尿病患者中下调心血管疾病，即白介素10(IL-10)和白介素4(IL-4)。我们将在去大脑中检查，非麻醉大鼠对静止和间歇的升压、心脏加速器和交感神经活动的反应在药物阻断细胞因子受体之前和期间的收缩。建议数实验还将量化这些循环细胞因子潜在的上调或下调的可能性多重检测中的血清样本。我们预计，这些实验将提供有关促炎和抗炎细胞因子在糖尿病自主循环控制中的作用在锻炼的时候。*本补充文件的范围不变。