Aspirin increases the human hypothalamic-pituitary-adrenal axis response to naloxone stimulation.
Prostaglandins are believed to influence hypothalamic-pituitary-adrenal (HPA) axis function, but their specific effects on ACTH and cortisol secretion in humans are unclear. Acetylsalicylic acid (aspirin) blocks the synthesis of prostaglandins from arachidonic acid. We studied the effects of oral aspirin on the plasma ACTH and cortisol responses to iv naloxone, which increases endogenous CRH release, in six normal volunteers and on the adrenocortical response to synthetic ACTH boluses in seven other healthy subjects, using placebo-controlled, single blinded protocols. Aspirin pretreatment significantly increased the ACTH response to naloxone [mean peak increase from basal, 8.3 +/- 1.2 vs. 5.9 +/- 0.8 pmol/L (P < 0.05); mean integrated response, 431.9 +/- 51.5 vs. 295.1 +/- 26.6 pmol/L.min (P < 0.005); for aspirin/naloxone and placebo aspirin/naloxone, respectively]. However, the corresponding cortisol results did not show statistically significant differences (P < 0.20). The mean integrated ACTH and cortisol responses were 46% and 26% greater with aspirin, respectively. Aspirin did not influence the cortisol responses to synthetic ACTH administration given according to a dose-response protocol. We conclude that aspirin augments the HPA axis response to naloxone stimulation in normal humans without having a direct effect at the adrenal level. The action of aspirin on the human HPA axis is probably mediated via inhibition of cyclooxygenase, resulting in changes in arachidonic acid metabolites, which influence ACTH release from corticotrophs.
Hockings
G I
GI
University of Queensland Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
Grice
J E
JE
Crosbie
G V
GV
Walters
M M
MM
Jackson
A J
AJ
Jackson
R V
RV
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000502:physiology; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009270:Naloxone / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology; D016037:Single-Blind Method; D013997:Time Factors
D011453:Prostaglandins; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D001241:Aspirin; D006854:Hydrocortisone