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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035195-02
Application #
3348869
Study Section
(SRC)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
McCubbin, J A; Bruehl, S; Wilson, J F et al. (1998) Endogenous opioids inhibit ambulatory blood pressure during naturally occurring stress. Psychosom Med 60:227-31
Bruehl, S; Carlson, C R; Wilson, J F et al. (1996) Psychological coping with acute pain: an examination of the role of endogenous opioid mechanisms. J Behav Med 19:129-42
McCubbin, J A; Wilson, J F; Bruehl, S et al. (1996) Relaxation training and opioid inhibition of blood pressure response to stress. J Consult Clin Psychol 64:593-601
McCubbin, J A; Lawson, E J; Cox, S et al. (1996) Prenatal maternal blood pressure response to stress predicts birth weight and gestational age: a preliminary study. Am J Obstet Gynecol 175:706-12
Glover, H (1995) A different opinion regarding the use of opiate antagonists in PTSD: comments on ""An unusual reaction to opioid blockade with naltrexone in a case of post-traumatic stress disorder"". J Trauma Stress 8:483-9
Ibarra, P; Bruehl, S P; McCubbin, J A et al. (1994) An unusual reaction to opioid blockade with naltrexone in a case of post-traumatic stress disorder. J Trauma Stress 7:303-9
McCubbin, J A; Bruehl, S (1994) Do endogenous opioids mediate the relationship between blood pressure and pain sensitivity in normotensives? Pain 57:63-7
Bruehl, S; McCubbin, J A; Wilson, J F et al. (1994) Coping styles, opioid blockade, and cardiovascular response to stress. J Behav Med 17:25-40
McCubbin, J A; Kaplan, J R; Manuck, S B et al. (1993) Opioidergic inhibition of circulatory and endocrine stress responses in cynomolgus monkeys: a preliminary study. Psychosom Med 55:23-8
McCubbin, J A (1993) Stress and endogenous opioids: behavioral and circulatory interactions. Biol Psychol 35:91-122

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