NEURAL MECHANISMS IN CARDIORENAL REGULATION

心脏调节的神经机制

• 批准号: 6564926
• 负责人: THOMAS E LOHMEIER
• 金额: $ 23.31万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564926
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; baroreceptors; baroreflex; blood pressure; blood volume; cardiovascular function; denervation; dietary sodium; dogs; electrolyte balance; neuroendocrine system; neuroregulation; norepinephrine; nutrition related tag; renin angiotensin system; salt intake; saluresis; sympathetic nervous system; urine

The role of the sympathetic nervous system (SNS) in long-term control of sodium excretion and arterial pressure is poorly understood. Nonetheless, it is recognized that increased sympathetic activity plays a role in the pathogenesis of salt and water retention in chronic sodium-retaining states including congestive heart failure, hepatic cirrhosis, and nephrotic syndrome, and in some forms of hypertension. Although the afferent mechanisms which mediate increased sympathetic activity in these disease states have not been established, baroreflex dysfunction is often an associated finding and has been hypothesized to account for chronic sympathoexcitation. In recent studies, we have found that chronic increments in salt intake and chronic angiotensin II (ANG II)- hypertension lead to sustained suppression of renal sympathetic activity (RSA) that promotes sodium excretion, suggesting that the SNS may contribute to long-term regulation of sodium balance and arterial pressure. The proposed studies will determine the afferent mechanisms which account for sustained inhibition of RSA during chronic increments in salt intake and chronic ANG II-hypertension, with particular emphasis on cardiopulmonary reflexes, which are especially important in suppressing RSA and promoting sodium excretion during acute increments in body fluids volumes. Another important goal will be to determine whether abolition of both sinoaortic and cardiopulmonary reflexes leads to salt-sensitive hypertension and exacerbation of ANG II-hypertension. To avoid extrapolating the finds from acute manipulations of the SNS to the chronic state, multiple techniques will be used in chronically instrumented dogs to directly examine the temporal effects of the renal sympathetic nerves on sodium excretion. These techniques include measurement of renal norepinephrine spillover as an index of changes in RSA and use of the split bladder preparations with permits simultaneous 24-h urine collection from an intact and denervated kidney. Additionally, alterations in afferent input into the central nervous system will be achieved by deafferentation of sinoaortic baroreceptors and cardiopulmonary receptors, and by control of plasma levels of ANG II. Thus, the proposed studies will directly test the hypothesis that neural-and/or hormonal-mediated renal sympathoinhibition is importantly involved in the chronic feedback regulation of body fluid volumes and arterial pressure under normal conditions and in hypertension.

交感神经系统（SNS）在长期控制中的作用 对钠排泄和动脉压了解甚少。尽管如此， 已经认识到增加的交感神经活动在神经系统的病理学改变中起作用。 慢性钠潴留水盐潴留的发病机制 包括充血性心力衰竭、肝硬化和 肾病综合征和某些形式的高血压。虽然 传入机制，介导增加交感神经活动，在这些 疾病状态尚未建立，压力反射功能障碍通常 一个相关的发现，并已被假设为解释慢性 交感神经兴奋在最近的研究中，我们发现， 盐摄入量增加和慢性血管紧张素II（ANG II）- 高血压导致肾交感神经活性持续抑制 (RSA)促进钠排泄，这表明SNS可能 有助于长期调节钠平衡和动脉 压力拟议的研究将确定传入机制 这解释了RSA在慢性增量期间的持续抑制， 盐摄入和慢性血管紧张素II高血压，特别强调 心肺反射，这是特别重要的抑制 RSA和促进体液急性增加时的钠排泄 卷另一个重要目标是确定是否废除 窦主动脉和心肺反射都导致盐敏感性 高血压和ANG II-高血压恶化。避免 将SNS急性操作的结果外推至慢性 在美国，多种技术将用于长期内固定犬 直接检查肾交感神经的时间效应 对钠排泄的影响这些技术包括测量肾脏 去甲肾上腺素溢出作为RSA变化的指标， 允许同时收集24小时尿液的分裂膀胱制备 一个完整的去神经的肾脏此外， 进入中枢神经系统的传入输入将通过 窦主动脉压力感受器和心肺感受器的去传入， 并通过控制ANG II的血浆水平。因此，拟议的研究将 直接检验神经和/或泌尿系统介导的肾 交感神经抑制在慢性反馈中起重要作用 正常情况下体液容量和动脉压的调节 条件和高血压。