CHRONIC NEURAL CONTROL OF BLOOD PRESSURE

中枢神经系统（CNS）在动脉血压的调节中起着关键作用，中枢神经控制的异常可能导致高血压或在其他因素的作用下使个体易患高血压。在当前资助期进行的研究强调了中枢神经系统在不依赖压力感受器的血压长期控制中的作用。这些研究集中在延髓吻侧腹外侧（RVLM）神经元在维持交感血管舒张性张力驱动中的作用尚不清楚。在目前的资助期内，我们发现RVLM中兴奋性氨基酸神经递质（EAA）的阻断受体降低血压的程度与完全自主神经阻断相同，前提是尾端腹外侧延髓中的神经元受到抑制。主要基于这一观察，我们提出了一种假设，即对RVLM的紧张性活跃的eaa介导的输入可以激发RVLM-交感兴奋性神经元，同时通过经尾侧腹侧髓质的回路激发这些神经元的抑制性输入。此外，我们假设RVLM的兴奋性和抑制性输入之间的平衡-由eaa介导的RVLM输入张力控制的交感神经兴奋性神经元控制交感血管舒张性的长期控制，这种平衡的改变可能导致高血压。此外，基于初步的数据，我们提出，对RVLM的紧张性活跃的eaaa介导的输入来自脑桥网状结构的特定区域。为了验证这些假设，我们提出了一系列在麻醉和清醒大鼠中进行的实验。大多数实验包括记录血压和交感神经活动，同时通过显微注射神经活性药物改变脑干不同区域的功能。五个具体目标将被解决：b[1]进一步研究eaa介导的RVLM输入在交感血管舒张性张力的强直调节中的作用；[2]以确定对RVLM的张力活性eaa介导的输入是否源于脑桥网状结构；[3]以确定在慢性缺乏压力感受器向大脑的反馈时，是否会改变强直活性eaa介导的RVLM输入的作用；[4]以确定在实验性高血压模型中，由eaa介导的张力活跃的RVLM输入驱动的RVLM交感兴奋神经元兴奋性和抑制性输入之间的平衡是否被改变；和[5]开始确定RVLM中C1神经元群在介导由RVLM的张力活动输入驱动的反应中的作用。这些研究将有助于我们对血压的神经控制的理解，从而可能为高血压的发病机制和治疗提供新的见解。

The central nervous system (CNS) plays a key role in regulation of arterial blood pressure and an abnormality of the central neural control may result in hypertension or predispose an individual to develop hypertension in response to other factors. Studies conducted the current grant period have highlighted the role of the CNS in baroreceptor- independent long-term control of blood pressure. These studies have focused on the role of neurons in the rostral ventrolateral medulla (RVLM) in maintaining the tonic drive of sympathetic vasomotor tones are unknown. During the current grant period we have found that blockade receptors for excitatory amino acid neurotransmitters (EAA) in the RVLM will reduce blood pressure to the same extend as total autonomic blockade provide that neurons in the caudal ventrolateral medulla are inhibited. Based primarily on this observation, we have developed the hypothesis that tonically active EAA-mediated inputs to the RVLM excite RVLM-sympathoexcitatory neurons and simultaneously excite inhibitory inputs to these neurons via a circuit through the caudal ventrolateral medulla. Furthermore, we hypothesize that this balance between excitatory and inhibitory inputs to RVLM- sympathoexcitatory neurons controlled tonically by EAA-mediated inputs to the RVLM governs the long-term control of sympathetic vasomoter tone, and alteration of this balance may result in hypertension. Furthermore, based on preliminary data we proposed that the tonically- active EAA-mediated input to the RVLM comes from a specific region of the pontine reticular formation. To test these hypothesis, we propose a series of experiments to be conducted in anesthetized as well as conscious rats. Most experiments involved recording blood pressure and sympathetic nerve activity while altering the function of discrete regions of the brain stem by microinjection of neuroactive drugs. Five specific aims will be addressed: [1] to further examine the role of EAA-mediated inputs to the RVLM in the tonic regulation of sympathetic vasomotor tone; [2] to determine whether tonically-active EAA-mediated inputs to the RVLM originate from the pontine reticular formation; [3] to determine if the effects of tonically-active EAA-mediated inputs to the RVLM are altered in the chronic absence of baroreceptor feedback to the brain; [4] to determine whether the balance between excitatory and inhibitory inputs to RVLM sympathoexcitory neuron driven by tonically- active EAA-mediated inputs to the RVLM is altered in models of experimental hypertension; and [5] to begin to determine the role of the C1 population of neurons in the RVLM in mediating the responses driven by tonically-active inputs to the RVLM. These studies will contribute to our understanding of the neural control of blood pressure, and therefore may provide new insight to the pathogenesis and treatment of hypertension.