Aspirin inhibits vasopressin-induced hypothalamic-pituitary-adrenal activity in normal humans

PGs influence ACTH secretion. However, their specific role in modulating the activity of the human hypothalamic-pituitary-adrenal (HPA) axis remains unclear. Acetylsalicylic acid (aspirin) inhibits the synthesis of PGs from arachidonic acid by blocking the cyclooxygenase pathway. In this study we ad...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 1997-03, Vol.82 (3), p.812-817
Main Authors: NYE, E. J, HOCKINGS, G. I, GRICE, J. E, TORPY, D. J, WALTERS, M. M, CROSBIE, G. V, WAGENAAR, M, COOPER, M, JACKSON, R. V
Format: Article
Language:English
Subjects:
Adolescent
Adrenocorticotropic Hormone - blood
Adult
Arginine Vasopressin - antagonists & inhibitors
Arginine Vasopressin - pharmacology
Aspirin - pharmacology
Biological and medical sciences
Cyclooxygenase Inhibitors - pharmacology
Functional investigation of endocrine glands and genital system
Humans
Hydrocortisone - antagonists & inhibitors
Hydrocortisone - blood
Hypothalamo-Hypophyseal System - drug effects
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Pituitary-Adrenal System - drug effects
Reference Values
Single-Blind Method
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Summary:PGs influence ACTH secretion. However, their specific role in modulating the activity of the human hypothalamic-pituitary-adrenal (HPA) axis remains unclear. Acetylsalicylic acid (aspirin) inhibits the synthesis of PGs from arachidonic acid by blocking the cyclooxygenase pathway. In this study we administered a single, clinically relevant dose of aspirin before HPA axis stimulation by a bolus dose of iv arginine vasopressin (AVP) to seven normal males using a randomized, placebo-controlled, single blinded design. Aspirin significantly reduced the cortisol response to AVP [mean peak increase from basal, 221.1 +/- 20.1 vs. 165.4 +/- 22.5 nmol/L (P = 0.0456); mean integrated response, 11,199.3 +/- 1,560.0 vs. 6,162.3 +/- 1,398.6 nmol.min/L (P = 0.0116) for placebo aspirin/AVP and aspirin/ AVP, respectively]. The ACTH response was reduced, but did not reach statistical significance [mean peak increase from basal, 7.5 +/- 2.2 vs. 4.3 +/- 0.3 pmol/L (P = 0.0563); mean integrated response, 142.6 +/- 36.0 vs. 96.2 +/- 8.7 pmol.min/L (P = 0.12) for placebo aspirin/ AVP and aspirin/AVP, respectively]. PGs may influence ACTH secretion by being stimulatory or inhibitory to the HPA axis at different levels, such as hypothalamic or pituitary. Which effect predominates in vivo during dynamic activation of the axis may depend on the level at which the secretory stimulus acts. We showed that when normal male volunteers were treated with the PG synthesis inhibitor, aspirin, they had a blunted HPA axis response to the pituitary corticotroph stimulator, AVP.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.82.3.812