Altered Baroreflex Responses by Dietary Sodium

膳食钠改变压力反射反应

• 批准号: 6652676
• 负责人: STEVEN BEALER BEALER
• 金额: $ 15万
• 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 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652676
• 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.

本研究项目的沿着目标是了解膳食钠改变压力反射敏感性的机制。增加钠摄入逆转急性、中度钠负荷诱导的心脏和神经压力感受性反射反应的易化。需要检验的假设是：钠摄入量增加会使中枢交感-肾上腺回路敏感，因此血浆钠的急性增加，作用于或通过正中视前核的神经元和α-肾上腺素受体，增加心脏和神经交感神经张力，抵消血管加压素的交感神经抑制剂作用，并降低压力反射敏感性。具体目标将确定增加钠摄入量的影响; 1）在急性钠负荷期间交感神经和副交感神经系统对心脏压力反射反应的贡献，2）在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）正中视前核中的神经元和5）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中的作用，3）加压素对压力反射功能的交感神经抑制作用，以及4）神经元，和5）在急性、中度钠负荷期间，中间视前核中的α-肾上腺素能受体介导压力反射敏感性。这些研究将在急性、中度钠负荷之前和之后的压力反射测试期间直接测量清醒、无限制大鼠的血压、心率、肾交感神经活动和腰神经活动。此外，将在急性钠负荷前后测量血管加压素和去甲肾上腺素的血浆浓度。将来自正常钠饮食动物的数据与提供等渗盐水作为唯一饮用流体以增加饮食钠三周的大鼠进行比较。将通过比较对照动物与给予该脑区神经毒性病变或在试验前用选择性α-肾上腺素能拮抗剂处理的大鼠的反应，评价神经元和α-肾上腺素能受体在正中视前核中的作用。定义这些机制将增加我们对某些心血管病理的理解。例如，压力反射缓冲减弱可能直接导致或至少允许实验动物和易感人群中慢性盐诱导高血压的建立。此外，以交感神经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，增加钠摄入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。本工作将在田纳西大学生理学系（孟菲斯，TN 38163）进行。

项目成果

Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion.

膳食钠的增加会改变静脉 ANG II 输注过程中血压的神经控制。

• DOI: 10.1152/ajpheart.00628.2002
• 发表时间: 2003
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Bealer,StevenL

Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy.

• DOI: 10.1016/j.jacc.2009.11.020
• 发表时间: 2010-02-09
• 期刊: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
• 影响因子: 24
• 作者: Xu, Tianhong;Yang, Zhao;Vatta, Matteo;Rampazzo, Alessandra;Beffagna, Giorgia;Pillichou, Kalliopi;Scherer, Steven E.;Saffitz, Jeffrey;Kravitz, Joshua;Zareba, Wojciech;Danieli, Gian Antonio;Lorenzon, Alessandra;Nava, Andrea;Bauce, Barbara;Thiene, Gaetano;Basso, Cristina;Calkins, Hugh;Gear, Kathy;Marcus, Frank;Towbin, Jeffrey A.
• 通讯作者: Towbin, Jeffrey A.

Increased dietary sodium inhibits baroreflex-induced bradycardia during acute sodium loading.

增加膳食钠可抑制急性钠负荷期间压力感受反射引起的心动过缓。

• DOI: 10.1152/ajpregu.00244.2004
• 发表时间: 2005
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Bealer,StevenL