BRAINSTEM GABA NEURONS IN EXPERIMENTAL HYPERTENSION

中枢神经系统在调节血管紧张素转换酶活性方面起着关键作用。 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 高血压的维持。三个脑干区域是关键 在血压调节中的重要性：头端延髓腹外侧 (RVL)、延髓尾侧腹外侧核(CVL)和核 孤束(NTS)。药理学的最新数据 研究表明，强直活动的GABA能突触 这些地区对英国石油公司产生了影响。这些实验的目的是 在本提案中描述的是研究GABA能的作用 下丘脑NTS、RVL和CVL的神经传递调节 BP和确定是否改变了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理 研究影响GABA能的药物的途径 当神经传递影响血压和心率时 直接注入NTS、RVL或CVL。这些研究 将主要关注间接作用的GABA的影响 激动剂，因为对这类药物的反应应该反映 GABA能神经传递的持续水平。对以下问题的回应 这些药物将在高血压患者和正常血压患者中进行比较。 老鼠。 第二组研究将使用神经化学方法来 研究类似的问题。在这些研究中，GABA的比率 合成(可能反映了GABA释放的速率 进入突触)将通过测量 局部抑制ITS后GABA的积累 新陈代谢。推拉式灌流技术将用于 确认观察到的合成变化确实反映了 GABA释放。使用这些技术，将确定 心血管传入活动的变化是否会影响 在NTS、RVL或CVL的GABA能神经传递。这些 技术也将被应用于确定GABA能 神经递质在NTS、RVL或CVL中发生改变 大鼠实验性高血压。 这些研究将提供对GABA能的全面分析 NTS、RVL和CVL的神经传递与 血压调节与高血压的发病机制。 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，并可能 因此，为治疗或预防糖尿病提供了新的见解 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.