BRAINSTEM GABA NEURONS IN EXPERIMENTAL HYPERTENSION

中枢神经系统在调节 心血管系统和改变的中枢神经控制 血压（BP）可能参与启动或 维持高血压。 三个脑干区域是关键 在血压调节中的重要性：延髓头端腹外侧 (RVL)、尾侧延髓腹外侧区（CVL）和核 孤束（NTS）。 药理学的最新数据 研究表明，在每个神经元中， 这些区域的变化影响BP。 实验的目的是 本提案中描述的是研究GABA能的作用， NTS、RVL和CVL中的神经传递在调节 并确定是否改变了GABA能 这些区域的神经传递可能参与了 高血压的发病机制 第一组实验将使用一种药物 研究药物如何影响GABA能的方法 神经传递影响血压和心率， 直接施用到NTS、RVL或CVL中。 这些研究 将主要集中在间接作用的GABA的影响 激动剂，因为对这些药物的反应应反映 持续的GABA能神经传递水平。 responses to 这些药物将在高血压和正常血压中进行比较 大鼠 第二组研究将使用神经化学方法， 研究类似的问题。 在这些研究中，GABA 合成（这可能反映了GABA释放的速率 将被测量， GABA的积累后，其局部抑制 新陈代谢. 将使用推拉灌注技术， 确认观察到的合成变化确实反映了 GABA释放 利用这些技术， 心血管传入活动的变化是否影响 NTS、RVL或CVL中的GABA能神经传递。 这些 技术也将被应用于确定是否GABA能 神经传递在NTS，RVL或CVL中发生改变， 大鼠实验性高血压。 这些研究将提供一个全面的分析GABA能 NTS，RVL和CVL中的神经传递与 调节血压和高血压的发病机制。 预计这些研究将提供新的和重要的 关于大脑在高血压中的作用的信息，可能 因此，为治疗或预防 高血压

The central nervous system plays a key role in the regulation of the cardiovascular system and altered central neural control of blood pressure (BP) may participate in the initiation or maintenance of hypertension. Three brainstem areas are of key importance in BP regulation: the rostral ventrolateral medulla (RVL), the caudal ventrolateral medulla (CVL), and the nucleus tractus solitarius (NTS). Recent data from pharmacological studies indicate that tonically active GABAergic synapses in each of these regions influence BP. The goal of the experiments described in this proposal is to study the role of GABAergic neurotransmission in the NTS, RVL, and CVL in the regulation of BP and to determine whether altered GABAergic neurotransmission in these regions may be involved in the pathogenesis of hypertension. The first set to experiments will utilize a pharmacological approach to study how drugs which influence GABAergic neurotransmission affect blood pressure and heart rate when administered directly into the NTS, RVL, or CVL. These studies will focus primarily on the effects of indirect-acting GABA agonists, since the responses to such drugs should reflect the ongoing level of GABAergic neurotransmission. Responses to these drugs will be compared in hypertensive and normotensive rats. The second set of studies will use a neurochemical approach to examine similar questions. In these studies, the rate of GABA synthesis (which presumably reflects the rate of GABA released into the synapse) will be determined by measuring the accumulation of GABA following local inhibition of its metabolism. A push-pull perfusion technique will be used to confirm that observed changes in synthesis do reflect changes in GABA release. Using these techniques, it will be determined whether changes in cardiovascular afferent activity affect GABAergic neurotransmission in the NTS, RVL, or CVL. These techniques will also be applied to determine whether GABAergic neurotransmission is altered in the NTS, RVL, or CVL in experimental hypertension in rats. These studies will provide a comprehensive analysis of GABAergic neurotransmission in the NTS, RVL, and CVL as related to the regulation of blood pressure and the pathogenesis of hypertension. It is expected that these studies will provide new and important information on the role of the brain in hypertension, and may therefore offer new insights into the treatment or prevention of hypertension.