Altered Baroreflex Responses by Dietary Sodium

本研究项目的主要目标是了解饮食钠改变压力反射敏感性的机制。增加钠摄入量对急性、中度钠负荷引起的心脏和神经压力感受性反射反应的反向促进作用。需要检验的假设是：钠摄入量增加使中枢交感肾上腺回路敏感，因此血浆钠急剧增加，作用于或通过正中视前核神经元和α-肾上腺素受体，增加心脏和神经交感神经张力，盖过血管加压素的交感神经抑制作用，降低压力感受器的敏感性。所涉及的具体目标将确定钠摄入量增加对以下方面的影响：1)急性钠负荷时交感和副交感系统对心脏压力反射反应的贡献，2)急性钠负荷时交感肾上腺的激活和神经压力反射反应，3)加压素对压力反射功能的交感抑制作用，以及4)急性中等钠负荷时正中核视前核神经元和5)α-肾上腺素能受体在调节压力反射敏感性中的作用，3)血管加压素对压力反射功能的交感抑制效应，以及4)神经元的作用，以及5)正中核视前核α-肾上腺素能受体在急性中等钠负荷时调节压力反射敏感性的作用。这些研究将在压力反射测试中直接测量清醒、无拘束的大鼠在急性中等钠负荷前后的血压、心率、肾交感神经活动和腰神经活动。此外，还将测量急性钠负荷前后血浆中加压素和去甲肾上腺素的浓度。来自正常钠饮食的动物的数据将与提供等渗盐水作为唯一饮料液的大鼠进行比较，以增加饮食中的钠三周。将通过比较对照组动物对给予该脑区神经毒性损伤的大鼠的反应，或在测试前使用选择性α-肾上腺素能拮抗剂治疗的反应，来评估神经元和α-肾上腺素能受体在正中视前核中的作用。明确这些机制将增加我们对一些心血管病理的理解。例如，压力感受性反射缓冲的减少可能直接导致或至少通过允许在实验动物和易感人类中建立慢性盐源性高血压。此外，以交感神经优势增强为特征的心脏压力感受性反射反应减少，是猝死和心律失常的独立危险因素。因此，增加钠摄入量可能会降低压力反射敏感性，增加心脏交感神经功能，从而增加心律失常的风险。这项工作将在田纳西大学生理学系进行，田纳西大学，孟菲斯，田纳西大学，田纳西州，38163。

The along objectives of this research project are to understand the mechanisms through which dietary sodium modifies baroreflex sensitivity. Increasing sodium ingestion reverse facilitation of cardiac and neural baroreflex responses induced by acute, moderate sodium loading. The hypothesis to be tested is that: Increased sodium ingestion sensitizes central sympathoadrenal circuits, so acute increases in plasma sodium, acting at or through neurons and alpha-adrenoreceptors in the median preoptic nucleus, increases cardiac and neural sympathetic tone, overrides the sympathoinhibitor effects of vasopressin, and reduces baroreflex sensitivity. The specific aims addressed will determine the effects of increased sodium ingestion on; 1) the contribution of the sympathetic and parasympathetic systems to cardiac baroreflex responses during acute sodium loading, 2) sympathoadrenal activation and neural baroreflex responses during acute sodium loading, 3) the sympathoinhibitory effects of vasopressin on baroreflex function, and the role of 4) neurons and 5) alpha-adrenergic receptors in the median preoptic nucleus in mediating baroreflex sensitivity during acute, moderate sodium loading, 3) the sympathoinhibitory effects of vasopressin on baroreflex function, and the role of 4) neurons, and 5) alpha-adrenergic receptors in the median preoptic nucleus in mediating baroreflex sensitivity during acute, moderate sodium loading. These studies will directly measure blood pressure, heart rate, renal sympathetic nerve activity, and lumbar nerve activity in conscious, unrestrained rats during baroreflex testing before and following acute, moderate sodium loading. In addition, plasma concentrations of vasopressin and norepinephrine will be measured before and following acute sodium loading. Data from animals on a normal sodium diet will be compared to rats provided isotonic saline as the sole drinking fluid to increase dietary sodium for three weeks. The role of neurons and alpha-adrenergic receptors in the median preoptic nucleus will be evaluated by comparing responses of control animals to responses from rats given neurotoxic lesions of this brain area, or treated with selective alpha-adrenergic antagonists prior to testing. Defining these mechanisms will add to our understanding of some cardiovascular pathologies. For example, diminished baroreflex buffering may directly contribute to, or at least by permissive in, the establishment of chronic, salt-induced hypertension in experimental animals and in susceptible humans. In addition, reduced cardiac baroreflex responses, characterized by increased sympathetic dominance, as an independent risk factor for sudden death and cardiac arrhythmias. Therefore, increased sodium ingestion may increase risk for arrhythmias by decreasing baroreflex sensitivity and increasing cardiac sympathetic function. The work will be performed in the Department of Physiology, University of Tennessee, Memphis, TN 38163.