The beta-adrenergic blocking drugs, introduced clinically for the treatment of cardiovascular disorders, have a variety of behavioral and psychological effects. Despite the fact that these drugs are among the most widely prescribed in the U.S., the mechanisms and extent of these effects remain poorly understood. One part of the proposed research examines the effects of CNS-penetrating and non-CNS-penetrating beta-blockers on a) behavior pattern Type A which has been implicated as a risk factor for ischemic heart disease (IHD), b) motor and vigilance performance (reaction time), and c) other behavioral side effects (e.g., fatigue, impotence, mood changes, sleep disturbance, anxiety-reduction) which patients widely experience. Two small clinical trials will compare the effects of various beta-blockers in patients with mild to moderate essential hypertension. In these studies, two control groups will consist of patients on a diuretic or a placebo. The first study will compare the effects of chronic administration of propranolol with atenolol. A second study will examine the relationship of beta 1 selectivity to behavioral effects by comparing nadolol with atenolol treatments. A third study involves acute administration of a beta-blocker and a beta-agonist to healthy subjects and examines the role of sympathetic reactivity in potentiating Type A behavior. A fourth study compares the acute effects of propranolol with atenolol. The broad objectives of this research are to understand psychophysiological mechanisms responsible for the expression of Type A behavior (an established IHD risk factor), and behavioral and psychological effects of beta-blocking medications at clinically-administered dosages. In addition, this research will yield basic information of potential use in further developing applications of beta-blockers, in the control of anxiety, anger, and untoward side effects, and in elucidating a possible application of beta-blockers in the primary prevention of coronary disease.
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