Altered Baroreflex Responses by Dietary Sodium

本研究项目的长期目标是了解膳食钠改变气压反射敏感性的机制。钠摄入增加可逆转急性、中度钠负荷引起的心脏和神经压力反射反应。需要验证的假设是：钠摄入增加使中央交感神经肾上腺回路敏感，因此血浆钠的急性增加，作用于或通过中央视前核的神经元和α -肾上腺素受体，增加心脏和神经交感神经张力，超越抗利尿激素的交感神经抑制剂作用，并降低压力反射敏感性。所讨论的具体目标将决定钠摄入量增加对；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活化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)神经元和5)视前正中核α -肾上腺素能受体在急性中度钠负荷时介导压力反射敏感性的作用。3)抗利尿激素对压力反射功能的交感抑制作用，以及4)神经元和5)视前正中核α -肾上腺素能受体在急性、中度钠负荷下调节压力反射敏感性中的作用。这些研究将直接测量血压、心率、肾交感神经活动和腰神经活动，在清醒、不受约束的大鼠在急性、中度钠负荷前后进行压力反射测试。此外，血管加压素和去甲肾上腺素的血浆浓度将在急性钠负荷前后测量。研究人员将正常钠饮食动物的数据与连续三周只饮用等渗盐水以增加饮食钠的大鼠的数据进行比较。神经元和α -肾上腺素能受体在正中视前核中的作用将通过比较对照动物和大鼠对该脑区神经毒性病变的反应，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。确定这些机制将增加我们对一些心血管疾病的理解。例如，在实验动物和易感人群中，压力反射缓冲的减弱可能直接导致或至少允许慢性盐性高血压的建立。此外，以交感优势增强为特征的心脏压力反射反应降低是猝死和心律失常的独立危险因素。因此，钠摄入增加可能通过降低压力反射敏感性和增加心脏交感神经功能而增加心律失常的风险。这项工作将在田纳西州孟菲斯大学生理学系进行，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.