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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 3 812-817
Copyright © 1997 by The Endocrine Society

Clinical Studies

Aspirin Inhibits Vasopressin-Induced Hypothalamic-Pituitary-Adrenal Activity in Normal Humans1

Elisabeth J. Nye, Gregory I. Hockings, Jeffery E. Grice, David J. Torpy2, Margaret M. Walters, Georgina V. Crosbie, Monica Wagenaar, Michael Cooper and Richard V. Jackson

Department of Medicine, Neuroendocrine Research Unit, University of Queensland, Queensland, Australia

Address all correspondence and requests for reprints to: Associate Professor Richard V. Jackson, Neuroendocrine Research Unit, University Department of Medicine, Greenslopes Private Hospital, Greenslopes, Brisbane, Queensland 4120, Australia.

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.




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