Endogenous opiates may influence the pathogenicity of stress. A series of studies are proposed to explore the hypothesis that failure of an opioidergic sympatho-inhibitory pathway may exaggerate responses to stress and increase risk for hypertension. Newly discovered opiate peptide systems provide several mechanisms for regulation of sympathetic neuronal function, and these systems may be important in the expression of cardiovascular risk. Failure of an opioidergic sympathoinhibitory pathway could intensify the pathogenicity of stress. The proposed studies are designed to determine the role or naloxone-sensitive opiate receptors in cardiovascular, neuroendocrine and behavioral responses to stress in young people with and without enhanced risk for hypertension. Two hundred healthy, young adult males will have blood pressures and family medical histories taken on campus. Individuals with casual pressures above the 80th percentile and with at least one parent with hypertension will be defined at enhanced risk while individuals with casual pressures from 20th to 80th percentile with no parental hypertension will be defined as at no enhanced risk. Selected subjects from both groups will be brought into the lab for conter-balanced, placebo-controlled, double-blinded stress tests. Specific goals are: 1) to determine the effects of the opiate antogonist, naloxone, on cardiovascular responses to behavioral stress (mental arithmetic) in young adults with and without enhanced risk or hypertension, 2) to determine the effects of naloxone on neuroendocrine responses to stress in young adults with and without enhanced risk, 3) to examine the effects of naloxone on task performance and subjective reactivity in young adults with and without enhanced risk. The magnitude of hemodynamic response to stress is known to correlate with several indicators of risk for hypertension. If opiates are involved in these response patterns, then opioid neurotransmission may have a casual or synergistic role in developmental pathophysiology of hypertension. A known relationship between opioid function and the pathogenicity of stress would stimulate important new strategies for pharmacological and behavioral intervention in hypertension during the early stages of the disease.
