Opiate peptide abnormalities have recently been described in patients with established idiopathic hypertension as well as in young adults at risk for hypertension. These abnormalities may exaggerate sympathoadrnomedullary and blood pressure responses to intense stimuli and may contribute to the development of hypertension. In normotensive young adults, the opiate antagonist naloxone increases blood pressure response to mental arithmetic stress. Young adults with mildly elevated casual blood pressure have exaggerated neuroendocrine and circulatory responses to arithmetic stressors, but naloxone has no detectable pressor effect in these individuals. Opiate systems can interact with blood pressure control mechanisms in two basic ways: 1) directly through baroreflex control nuclei and peripheral sympathetic ganglia and 2) indirectly through supramedullary behavioral effects on cognitive/motivational response systems. The present proposal is designed to examine the neurobehavioral level of interaction between naloxone-sensitive opiate systems and blood pressure control mechanisms by comparison of the effects of naloxone on responses to an active, coping type stressor, mental arithmetic, with a non-noxious, baroreflex challenge, orthostatic stress. Healthy, young adult males will have casual blood pressures and family medical histories taken. Individuals with casual pressures above the 80 th percentile and with at least one parent with hypertension will be defined at enhanced risk while individuals with pressures below the 80th percentile with no parental hypertension will be defined at no enhanced risk. Selected subjects will be brought to the lab for placebo-controlled, counterbalanced, double-blinded stress tests. If opiate pathways interact directly with baroreflex nuclei or sympathetic ganglia, then naloxone should have a positive-pressor effect on responses to orthostatic stress as well as mental arithmetic in low risk subjects. If opiates affect blood pressure responses indirectly through congnitive/motivational mechanisms, then there should be no effect of naloxone on responses to orthostatic stress. Comparison of responses to the stressors in individuals with high and low casual blood pressure will enable a more precise characterization of the mechanism of opiate dysfunction in the expression of risk for hypertension.
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