GABA-ERGIC MECHANISMS INFLUENCING VASOPRESSIN RELEASE

影响加压素释放的 GABA 能机制

• 批准号: 3344560
• 负责人: Joseph R Haywood
• 金额: $ 5.26万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3344560
• 关键词: baroreceptors; blood pressure; body fluid osmolarity; captopril; cardiac output; gamma aminobutyrate; ganglionic blocking agents; heart rate; hemodynamics; hypertension; neuropharmacology; prosencephalon; vascular resistance; vasopressins

Previous work in this laboratory has shown that GABA blocks the osmotic stimulation of vasopressin release. The hypothesis that will be tested in this proposal is that GABA or the pharmacological activation of the endogenous forebrain GABAergic system is capable of interfering with both osmotic and baroreceptor stimulated vasopressin release mechanisms. A corollary hypothesis that will be examined is that GABA asserts a tonic inhibition on the vasopressin system as part of the baroreflex pathway. During osmotic and baroreceptor activated vasopressin release, vasopressin levels and changes in arterial pressure, heart rate, cardiac output and total peripheral resistance will be monitored. To limit the distribution of centrally administered GABA to the forebrain, a cold cream plug will be placed in the posterior third ventricle. The first study will examine GABA interactions with osmotic stimuli. Acutely anephric rats will be infused with hypertonic sodium chloride to stimulate osmotic activated vasopressin release. In the second study, baroreceptor mediated vasopressin release will be stimulated with sequential administration of captopril (a renin-angiotensin system antagonist) and a ganglionic blocking agent (a sympathetic nervous system antagonist) to lower arterial pressure. In both of these studies, GABA, an uptake inhibitor of GABA (nipecotic acid), or a metabolism inhibitor of GABA (Gamma-vinyl GABA) will be given to assess the effect on plasma vasopressin levels and systemic hemodynamics. The third study will focus on the role of GABA in the tonic inhibition of vasopressin release through a baroreflex mechanism. Local injections of the GABA antagonist, bicuculline, into the supraoptic nucleus, will be used to investigate this action. These studies will contribute significantly to an understanding of the role of the GABAergic system in modulating vasopressin release.

该实验室以前的工作表明，GABA阻断了渗透压， 刺激血管加压素释放。 这个假设将在 这一建议是，GABA或药理学激活的 内源性前脑GABA能系统能够干扰这两者 渗透压和压力感受器刺激的加压素释放机制。 一 一个必然的假设，将被检查是，GABA断言一个滋补品 对作为压力反射途径的一部分的加压素系统的抑制。 在渗透压和压力感受器激活的加压素释放过程中， 动脉压、心率、心输出量和 将监测总外周阻力。 为了限制分布 的集中管理GABA的前脑，冷奶油塞将 位于第三脑室后部。 第一项研究将检查GABA 与渗透压刺激的相互作用。 急性无肾大鼠将输注 用高渗氯化钠刺激渗透压激活的加压素 release. 在第二项研究中，压力感受器介导的加压素释放 将通过连续施用卡托普利（a 肾素-血管紧张素系统拮抗剂）和神经节阻滞剂（A 交感神经系统拮抗剂）降低动脉压。 无论是 在这些研究中，GABA，一种GABA（哌啶甲酸）的摄取抑制剂，或 将给予GABA代谢抑制剂（γ-乙烯基GABA）以评估 对血浆血管加压素水平和全身血流动力学的影响。 第三 研究将集中于GABA在加压素的紧张性抑制中的作用 通过压力反射机制释放。 局部注射GABA 拮抗剂，荷包牡丹碱，进入视上核，将用于 调查这一行动。 这些研究将大大有助于 了解GABA能系统在调节血管加压素中的作用 release.