The present proposal will investigate the effects of antihypertensive drugs on sensory function, motor ability, learning and memory in baboons both when they are normotensive, and after an experimental hypertensive state has been induced. Clinical case reports of adverse behavioral side-effects of antihypertensive compounds have been frequent, leading many patients to discontinue medication. Unfortunately, both human and animal investigations have been equivocal as to the behavioral performance and sensory effects of frequently used drugs such as beta-blockers, and centrally acting antihypertensive compounds. Detailed information is lacking on the behavioral and sensory effects of diuretics, and on the newer antihypertensive compounds such as angiotensin-converting-enzyme inhibitors and calcium-channel blockers. The proposed project will use two baboon models of hypertension, a deoxycorticosterone acetate (DOCA)-salt model and a Goldblatt (two-kidney, one-clamp) model, to simulate low renin and high renin states of hypertension, respectively. The effects of five different classes of antihypertensive compounds will be examined in these two models with continuous blood pressure monitoring via implanted arterial catheters. Detailed assessments of both behavioral and central nervous system effects of these antihypertensive agents will be provided by having animals perform tasks designed to assess sensory and motor function as well as specific aspects of conditional learning and memory.
