Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist.

The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP-A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa.