BRAIN STEM MECHANISMS OF SALT SENSITIVE HYPERTENSION

饮食中过量的盐分是导致该病发生的主要因素 高血压的严重程度。然而，盐的确切机制(S) 对高血压严重程度的影响尚不清楚。所在地区 延髓头端腹外侧区(RVLM)是脑干的主要部位 对中枢调节动脉血压至关重要 神经系统(CNS)。这个实验室最近的研究表明 过量的食盐(氯化钠)摄入特异地敏化血管运动 RVLM神经元对兴奋性刺激的反应。的长期目标是 本研究旨在确定RVLM的盐敏化作用 在高血压的发病机制中起重要作用。拟议的研究 将提供一致的证据来解决这个问题。这个 第一个具体目标是从参数上描述和确定 产生RVLM盐敏化的必要条件。这 将通过给大鼠喂食不同浓度的 饮食和测量加压和交感兴奋反应产生的 微量注射L-谷氨酸激活RVLM神经元这个 第二个具体目标是确定促进SALT的中枢神经系统机制-- RVLM的敏化。RVLM微量注射产生的反应 受体选择性药物将确定升压和 摄入过量氯化钠的大鼠交感兴奋反应一致 增强的，或者反应增强是否与特定的 神经递质受体。还将确定脑部损伤是否 已知可以预防盐依赖型高血压也可以预防盐 RVLM血管运动神经元的敏化。第三个具体目标是 研究RVLm的盐敏化与盐的关系。 依赖性实验性高血压。这将通过以下方式实现 测量心血管和交感神经兴奋性反应 刺激高血压大鼠的RVLM，并测定 慢性破坏RVLM神经元可以防止SALT的发展 依赖型高血压。拟议的研究将是首批 将已知的RVLM功能扩展到病理情况 血压正常的动物；并将对我们的 对食盐、高血压和高血压之间关系的认识 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.