ANTITHYPERTENSIVE DRUGS: BIOBEHAVIORAL EFFECTS

抗高血压药物：生物行为效应

• 批准号: 3346568
• 负责人: JAYLAN S TURKKAN
• 金额: $ 13.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346568
• 关键词: Cercopithecidae; alpha antiadrenergic agent; angiotensin /renin /aldosterone hypertension; antihypertensive agents; behavior test; beta antiadrenergic agent; blood chemistry; blood pressure; centrally acting drug; color visions; discrimination learning; disease /disorder model; diuretics; drug adverse effect; hypotension; memory; psychomotor reaction time; psychopharmacology; psychophysics; sleep; sleep disorders

Noncompliance by hypertensive patients with their medication regimens remains an important problem, and patient complaints leading to withdrawal from therapy frequently center on behavioral changes such as impairments of learning, memory, sensory and motor function. This project will systematically quantify the behavioral side-effects produced by antihypertensive compounds in both normotensive and hypertensive non-human primates (baboons). A series of studies in two hypertensive baboon models (renovascular and DOCA-salt-induced) will examine the behavioral effects of compounds prescribed clinically for hypertension control. The two model will be used as experimental tools to dissociate the behavioral effects of antihypertensive agents from their BP-lowering effects. Specifically, the proposed studies will: 1) quantify sensory and psychomotor functions such as color discrimination and speed of motor responses; 2) examine commonly prescribed combinations of antihypertensive compounds such as diuretics in combination with beta-blockers or alpha-agonists for their separate and combined effects on behavioral performance and blood pressure levels; and 3) measure continuous activity during sleep and waking cycles as an index or sleep disturbances, displacement, and fragmentation produced by antihypertensive compounds. aCute and chronic auscultatory blood pressure changes will be monitored in awake animals throughout the protocols to evaluate the relationship between degree of hypotension and degree and type of behavioral effects produced. Plasma levels of hormones and electrolytes also will be measured to elucidate time-course of mechanism and metabolism. The proposed studies will generate data regarding the behavioral performance changes produced by antihypertensive medications, and thus provide systematic quantitative information relevant to clinical non- compliance issues as well.

高血压患者的药物治疗方案的不符合性 仍然是一个重要的问题，患者投诉导致撤离 从治疗经常以行为改变为中心，例如 学习，记忆，感觉和运动功能。 这个项目将 系统地量化由 异常和高血压非人类的降压化合物 灵长类动物（狒狒）。 在两种高血压狒狒模型中进行的一系列研究 （培养皿和Doca-salt诱导的）将检查 在临床上规定了用于高血压控制的化合物。 这两个模型 将用作实验工具，以解离 降压药的降压剂降低效果。 具体来说， 拟议的研究将：1）量化这种感觉和精神运动功能 作为运动响应的颜色歧视和速度； 2）通常检查 规定的降压化合物（例如利尿剂）的规定组合 与β受体障碍者或α-激动剂组合，将其独立 对行为表现和血压水平的结合影响；和 3）测量睡眠期间的连续活动，并唤醒循环作为指数 或睡眠障碍，位移和碎片 降压化合物。 急性和慢性神学血压 在整个协议中，将在清醒动物中监视更改 评估低血压程度与程度与类型之间的关系 产生的行为效应。 激素和电解质的血浆水平 还将衡量以阐明机制和代谢的时间。 提出的研究将生成有关行为的数据 降压药产生的性能变化，因此 提供与临床非临床无关的系统定量信息 合规性问题。