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

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。

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.