ENDOGENOUS OPIATES, STRESS AND RISK FOR HYPERTENSION

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Endogenous opioid peptides comprise an important neuroregulatory mechanism which can centrally integrate autonomic outflow. Young adults at risk for later development of hypertension show a pattern of exaggerated circulatory, sympathoadrenal and behavioral responses in both laboratory and naturalistic settings. Although extreme blood pressure fluctuations in young people may ultimately result in sustained hypertension, the biobehavioral mechanisms of their reactivity remain to be identified. Endogenous opioid peptides are released during behavioral stress and inhibit sympathetic nervous system responses. Their role in control of autonomic outflow and blood pressure has led to the hypothesis that defective opioidergic sympathoinhibition is responsible for blood pressure dysregulation in the early stages of hypertension. We have tested this hypothesis in our lab by examination of the effects of the opiate antagonist, naloxone on blood pressure responses to stress in young adults with high casual blood pressure. Results suggest that opioid inhibition of responses to stress directly influences blood pressure levels and may likewise influence risk for hypertension. Experimental verification of the latter is only now practical because of two recent technological advances. First, development of reliable, accurate, and unobtrusive portable blood pressure monitors now enables reasonable determination of ambulatory pressures in naturalistic settings. Second, recent FDA approval of the long-lasting oral opiate antagonist, Trexan, has made it possible to measure opioidergic influences on blood pressure during normal daily activities. The proposed studies are designed to confirm and extend previous work by examination of two related questions: 1) Does opioid inhibition of laboratory reactivity reflect opioid control of ambulatory pressures in naturalistic settings? 2) Do behaviors which reduce stress reactivity operate via opioidergic mechanisms? These studies are necessary to link existing laboratory findings to the developmental pathophysiology of hypertension so that behavior therapies can be more strategically designed to reduce blood pressure. Increased understanding of potentially therapeutic opioid mechanisms and opio-agonistic behaviors will enable better diagnosis and treatment of mild hypertension.