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.
