Altered Baroreflex Responses by Dietary Sodium

膳食钠改变压力反射反应

• 批准号: 6352512
• 负责人: STEVEN BEALER BEALER
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6352512
• 关键词: alpha adrenergic receptor; baroreflex; blood pressure; cardiovascular function; dietary sodium; experimental brain lesion; laboratory rat; neuroregulation; nutrition related tag; preoptic areas; vasopressins

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.

该研究项目的主要目标是了解膳食钠改变压力反射敏感性的机制。增加钠摄入量会逆转由急性、中等钠负荷引起的心脏和神经压力反射反应的促进。要检验的假设是：钠摄入量的增加会使中枢交感肾上腺回路变得敏感，因此血浆钠的急剧增加，作用于或通过正中视前核中的神经元和α-肾上腺素受体起作用，增加了心脏和神经交感神经张力，克服了交感神经抑制剂的作用。加压素，并降低压力反射敏感性。所涉及的具体目标将决定增加钠摄入量对以下方面的影响： 1) 急性钠负荷期间交感和副交感系统对心脏压力反射反应的贡献，2) 急性钠负荷期间交感肾上腺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) 神经元的作用5) 正中视前核中的α-肾上腺素能受体在急性、中度钠负荷期间介导压力反射敏感性， 3) 加压素对压力感受反射功能的交感抑制作用，以及 4) 神经元和 5) 正中视前核中的 α-肾上腺素受体在急性、中度钠负荷期间介导压力感受反射敏感性中的作用。这些研究将在急性、中度钠负荷前后进行压力反射测试时，直接测量清醒、不受约束的大鼠的血压、心率、肾交感神经活动和腰神经活动。此外，将在急性钠负荷之前和之后测量加压素和去甲肾上腺素的血浆浓度。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用液体以增加饮食钠三周的大鼠进行比较。通过将对照动物的反应与给予该脑区神经毒性损伤的大鼠的反应或在测试前用选择性α-肾上腺素能拮抗剂治疗的大鼠的反应进行比较，可以评估中视前核中神经元和α-肾上腺素能受体的作用。定义这些机制将增加我们对一些心血管病理学的理解。例如，压力感受反射缓冲的减弱可能直接导致或至少允许在实验动物和易感人群中形成慢性、盐诱发的高血压。此外，以交感神经优势增强为特征的心脏压力反射反应减弱，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并增加心脏交感功能，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（孟菲斯，TN 38163）进行。