AGING, ANTIHYPERTENSIVE THERAPY, AND BLOOD PRESSURE REGULATION

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Both aging and hypertension impair BP regulation, predisposing hypertensive elderly people to hypotension. Hypertension may also impair cerebral auto- regulation, making hypertensive elderly vulnerable to syncope and falls during stresses that reduce BP. During previous funding periods, we showed that i) BP elevation in elderly subjects is independently associated with orthostatic (OH) and postprandial (PPH) hypotension, ii) elderly nursing home residents successfully treated for hypertension have a lower prevalence of OH than those with uncontrolled hypertension, and iii) BP lowering with the calcium channel blocker nicardipine ameliorates PPH. In response to these findings we hypothesize the BP elevation impairs cerebral and systemic BP regulation in the elderly, and that the successful treatment of hypertension may improve adaptive cerebral and systemic regulatory responses to hypotensive stress. Rigorous testing of this hypothesis is important because many physicians are reluctant to treat hypertension in the elderly for fear of precipitating hypotension and syncope. The study will consist of 2 parts; i) a cross-sectional, between-group comparison of elderly normontensive (N=50), controlled hypertensive (N=50), controlled hypertensive (N=50), and uncontrolled hypertensive (N=70) subjects (>65 years), to determine the effects of hypertension on cerebral auto-regulation and systemic BP regulation, and ii) a prospective study of uncontrolled hypertensive to determine the effect of pharmacologic BP lowering for 6 months, on cerebral auto-regulation (using transcranial Doppler ultrasound during the Valsalva maneuver and head-up tilt), baroreflex function (phase IV of the Valsalva), pulsatile distensibility of the carotid artery, beat-to-beat recordings of Doppler carotid images and BP), and cardiovascular adaptation to orthostasis (cardiac output by CO2 rebreathing and pulse contour analysis, and forearm vasoconstriction by venous occlusion plethysmography). Data will be analyzed using multi-variate and repeated measures analyses of variance. The results of this study may greatly improve geriatric care if they show that judicious anti-hypertensive therapy reduces the risk of hypotension, syncope, and cerebral ischemia in hypertensive elders.