BRAINSTEM GABA NEURONS IN EXPERIMENTAL HYPERTENSION

中枢神经系统在动脉调节中起重要作用， 压力和大量的数据表明，大脑发挥着 在某些形式的高血压的发病机制中起关键作用。 几 先前的研究表明压力感受器的衰减 中枢神经系统内发生的反射有助于 某些实验性高血压的发展。 细胞核 孤束（NTS）是大脑中接收所有 来自外周压力感受器的输入，因此， 参与压力感受器反射的过程。 最近的数据 表明刺激NTS中GABA/B受体减弱了 压力感受性反射与GABA/B介导神经传递 NTS中的受体在某些形式的实验中是异常的。 高血压 因此，提出了增强的GABA/B- 在NTS介导的神经传递，通过产生一个中央 压力感受器反射减弱，有助于发病机制 在两种实验性高血压模型中， 自发性（遗传性）高血压大鼠和用 脱氧皮质酮和盐。 本提案所述的研究审查了 通过确定GABAB变化之间的关系， NTS中的受体，NTS中的GABA释放，心血管反应 将激动剂或拮抗剂药物注射到NTS中， GABA/B受体与高血压的发生。 额外 研究将检查参与这种GABA/B介导的机制， 压力感受器反射的衰减。 待检验的假设是 GABA作用于GABA/B受体， 压力感受器传入神经减弱神经递质的释放 来自压力感受器传入，这种机制是 压力感受器传入传递的频率依赖性抑制 的NTS。 预计这些研究将增加我们的 了解心血管功能的中枢神经控制 因为它与高血压有关， 治疗或预防高血压。

The central nervous system is important in the regulation of arterial pressure and an abundance of data suggests that the brain plays a critical role in the pathogenesis of some forms of hypertension. Several previous studies have suggested that an attenuation of the baroreceptor reflex occurring within the central nervous system contributes to the development of certain forms of experimental hypertension. The nucleus tractus solitarius (NTS) is the site in the brain which receives all of the input from peripheral baroreceptors, and therefore is prominently involved in the processing of the baroreceptor reflex. Recent data indicate that stimulation of GABA/B receptors in the NTS attenuates the baroreceptor reflex and that neural transmission mediated by GABA/B receptors in the NTS is abnormal in certain forms of experimental hypertension. Thus, the hypothesis is presented that enhanced GABA/B- mediated neural transmission in the NTS, by producing a central attenuation of the baroreceptor reflex, contributes to the pathogenesis of hypertension in two models of experimental hypertension, the spontaneously (genetic) hypertensive rat and the rat treated with deoxycorticosterone and salt. Studies described in this proposal examine this hypothesis by determining the relationship between changes in GABAB receptors in the NTS, GABA release in the NTS, cardiovascular responses to injection into the NTS of drugs which are agonists or antagonists at GABA/B receptors, and the development of hypertension. Additional studies will examine the mechanisms involved in this GABA/B-mediated attenuation of the baroreceptor reflex. The hypothesis to be tested is that GABA acting on GABA/B receptors present presynaptically on baroreceptor afferent nerves attenuates the release of neurotransmitter from baroreceptor afferents, and that this mechanism underlies the frequency-dependent inhibition of baroreceptor afferent transmission in the NTS. It is expected that these studies will increase our understanding of the central neural control of cardiovascular function as it relates to hypertension and may provide new insight into the treatment or prevention of hypertension.