BRAIN STEM MECHANISMS OF SALT SENSITIVE HYPERTENSION

过量的饮食盐是发病的主要因素， 高血压的严重程度。然而，盐的精确机制 导致高血压严重程度的因素尚不清楚。 的区域 延髓头端腹外侧区（RVLM）是脑干的主要部位 对于中枢神经系统调节动脉血压至关重要 神经系统（CNS）。 该实验室最近的研究表明， 过量的食盐（NaCl）摄入会使血管敏感 RVLM的神经元对兴奋性刺激的反应。 的长期目标 本研究旨在确定RVLM的盐敏感性是否 有助于高血压的发病机制。 拟议研究 将为解决这一问题提供一致的证据。 的 第一个具体目标将是参数化表征和建立 产生RVLM盐致敏所需的条件。 这 将通过给大鼠喂食不同浓度的NaCl来完成。 饮食和测量升压和交感神经兴奋反应产生的 使用L-谷氨酸的显微注射激活RVLM神经元。 的 第二个具体目标将确定中枢神经系统的机制，有助于盐- RVLM的敏感性。RVLM微量注射产生的反应 受体选择性药物将确定是否升压和 消耗过量NaCl的大鼠的交感神经兴奋反应是一致的， 增强，或者反应增强是否与特定的 神经递质受体 还将确定脑损伤是否 已知可预防盐依赖性高血压， RVLM血管神经元的敏化。 第三个具体目标将 研究RVLM的盐敏感性与盐的关系， 实验性高血压 这将通过 测量心血管和交感神经兴奋反应产生的 刺激高血压大鼠的RVLM，并确定是否 RVLM神经元的慢性破坏可以防止盐- 依赖性高血压 拟议的研究将是第一批 将已知的RVLM功能扩展到病理条件， 正常血压的动物;并将大大有助于我们的 了解饮食中的盐、高血压和 大脑

Excess dietary salt is a major contributing factor to the incidence and severity of hypertension. However, the precise mechanism(s) by which salt contributes to the severity of hypertension are unknown. The region of the rostral ventrolateral medulla (RVLM) is a principal brain stem locus critical for the regulation of arterial blood pressure by the central nervous system (CNS). Recent studies from this laboratory have shown that excess dietary salt (NaCl) consumption specifically sensitizes vasomotor neurons of the RVLM to excitatory stimulation. The long-term objective of this research is to determine if salt-sensitization of the RVLM contributes to the pathogenesis of hypertension. The proposed research will provide convergent lines of evidence to address this question. The first Specific Aim will be to parametrically characterize and establish the conditions necessary to produce salt-sensitization of the RVLM. This will be accomplished by feeding rats various concentrations of NaCl in the diet and measuring pressor and sympathoexcitatory responses produced by activation of RVLM neurons using microinjections of L-glutamate. The second Specific Aim will identify CNS mechanisms that contribute to salt- sensitization of the RVLM. Responses produced by RVLM microinjections of receptor-selective drugs will establish whether pressor and sympathoexcitatory responses of rats consuming excess NaCl are uniformly augmented, or whether response potentiation is associated with specific neurotransmitter receptors. It will also be determined if brain lesions known to prevent salt-dependent hypertension also prevent salt sensitization of RVLM vasomotor neurons. The third Specific Aim will examine the relationship of salt-sensitization of the RVLM to salt- dependent experimental hypertension. This will be accomplished by measuring cardiovascular and sympathoexcitatory responses produced by stimulation of the RVLM in hypertensive rats, and determining whether chronic destruction of RVLM neurons can prevent the development of salt- dependent hypertension. The proposed studies will be among the first to extend to pathological conditions what is known of RVLM function in normotensive animals; and will contribute significantly to our understanding of the relationship between dietary salt, hypertension, and the brain.