Effects of propranolol on symptom and endocrine responses to pentagastrin.
Intravenous injections of CCK-B agonists, such as pentagastrin, produce symptoms of panic and potent activation of the human hypothalamic-pituitary-adrenal (HPA) axis. It is unclear whether these psychological and endocrine effects are mediated by similar or independent processes. Independence is supported by prior evidence that beta-adrenergic receptor blockade attenuates cardiovascular and symptom but not vasopressin responses to CCK-4. To further explore associations between somatic, emotional and endocrine responses to CCK-B agents, and potential beta-adrenergic mediating mechanisms, symptom and endocrine responses to pentagastrin were examined after propranolol pre-treatment. Cardiovascular, symptom, and endocrine (ACTH, cortisol, epinephrine) responses to pentagastrin were measured in 16 healthy adult subjects randomly assigned to receive propranolol or placebo pre-treatment. Propranolol significantly blocked the normal cardiac acceleration produced by pentagastrin, but did not reduce panic symptom or anxiety effects. It delayed and perhaps enhanced the cortisol response. No relationship between HPA and symptom responses following pentagastrin could be detected, though pre-pentagastrin cortisol was inversely related to post-injection panic symptom intensity. Endocrine, cardiovascular and symptom responses to pentagastrin appear to be separately mediated, as they did not change in concert in response to propranolol pre-treatment, nor were they correlated with one another. The results are consistent with the presence of inhibitory beta-adrenergic mediation of the HPA axis in humans. They support the hypothesis that the HPA response to pentagastrin is not secondary to the psychological stress of its side effects.
Khan
Samir
S
Trauma, Stress and Anxiety Research Center, Department of Psychiatry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0118, USA.
Liberzon
Israel
I
Abelson
James L
JL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D016555:Matched-Pair Analysis; D009490:Neurosecretory Systems / Q000187:drug effects; D010200:Panic / Q000187:drug effects / Q000502:physiology; D010418:Pentagastrin / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D043887:Receptor, Cholecystokinin B / Q000819:agonists; D012016:Reference Values; D013223:Statistics as Topic
D000319:Adrenergic beta-Antagonists; D043887:Receptor, Cholecystokinin B; D011433:Propranolol; D010418:Pentagastrin; D006854:Hydrocortisone