The objectives of the proposed research are to continue the Principal Investigator's systematic study of altered opioidergic inhibition of sympathetic nervous system and cardiovascular reactivity during behavioral stress in the development of idiopathic essential hypertension. Opioid inhibition of blood pressure may also be important in the antihypertensive action of sympatholytic behavioral and pharmacological therapies. Four recent findings support this contention: 1) the pressor effect of the opioid antagonist, naloxone, is significantly diminished during behavioral stress in young adults at enhanced risk for hypertension, 2) plasma levels of beta-endorphin are significantly decreased in some groups of hypertensive patients, 3) chronic antihypertensive treatment with clonidine normalizes both blood pressure and beta-endorphin levels, and 4) the antihypertensive effect of clonidine is antagonized by naloxone in some hypertensive patients. Research is proposed to determine the role of endogenous opioid mechanisms in the pathophysiology of essential hypertension and to investigate the role of an hypothesized opioid-releasing mechanism in antihypertensive pharmacotherapy with clonidine. This will be accomplished by examination of the effects of naloxone on circulatory and neuroendocrine responses during rest and behavioral stress in unmedicated patients with mild, uncomplicated essential hypertension (compared with normative controls). The pressor effect of naloxone will be examined in subgroups of unmedicated hypertensive patients with and without signs of excessive sympathetic nervous system activity. The role of opioid mechanisms in the blood pressure-lowering effect of sympatholytic antihypertensive therapy will be determined by documenting changes in the pressor effect of naloxone after chronic medication with clonidine. Elucidation of opioid mechanisms of blood pressure dysregulation in hypertension will advance understanding of the diagnosis, pathophysiologic mechanisms, and optimum therapeutic strategies in this heterogeneous disease category.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL035195-05A1
Application #
3348866
Study Section
Behavioral Medicine Study Section (BEM)
Project Start
1988-09-30
Project End
1995-01-31
Budget Start
1992-02-25
Budget End
1993-01-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
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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