This is a request for an ADAMHA RSA. The long range goal is to elucidate biological mechanisms whereby such coronary-prone traits as Type A behavior and hostility play a role in the pathogenesis and course of coronary heart disease. In the context of research supported by my program project grant, this application focuses on two specific aims: 1) to increase our understanding of the potentially pathogenic biological correlates of hostility and anger; and 2) to document and explore further the nature of deficient parasympathetic antagonism of sympathetic effects on the heart, indexed by more prolonged EKG T-wave attenuation to isoproterenol infusion, in hostile Type A persons. To achieve aim 1, we shall determine whether subjects with high scores on the Cook-Medley Hostility (Ho) scale show enhanced cardiovascular and neuroendocrine reactivity when angered by harassment during a lab task. Four studies will be done, each with 52 subjects, half with high and half with low Ho scores. Age and gender effects will be examined by comparing samples of young and middle-aged men and women. To achieve aim 2, cardiovascular, electrophysiological (12-lead EKG), and neuroendocrine responses to isoproterenol infusions will be examined following placebo, vagal blockade (atropine), and vagal enhancement (neostigmine) pharmacological pretreatments. Subjects will be selected from the studies under aim 1, based on having the highest and lowest reactivity to harassment. Demonstration of hyperactivity to hostile/anger-prone subjects will document the biological plausibility of hostility as a coronary risk factor. The knowledge gained about coronary-prone behavior will help to develop more effective preventive treatment, and rehabilitation approaches. Professional growth, in terms of increased understanding of the social psychology of interpersonal conflict and of electrophysiologic techniques, will occur via new collaborative relationships in the proposed research.
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