ARGININE-VASOPRESSIN AND CORTICOTROPIN-RELEASING HORMONE ARE SEQUENTIALLY INVOLVED IN THE ENDOTHELIN-1-INDUCED ACUTE STIMULATION OF RAT PITUITARY-ADRENOCORTICAL AXIS

The acute effect of endothelin-1 (ET-1) on the hypothalamo-pituitary-a drenal (HPA) axis has been investigated in the rat. The plasma concent rations of arginine-vasopressin (AVP), ACTH, aldosterone and corticost erone have been measured by RIA 30 and 60 min after ET-1 administratio n. ET-1 (2.0 nmol kg(-1)) raised AVP plasma concentration at both 30 a nd 60 min. ET-1 did not alter the ACTH plasma level at 30 min, but mar kedly increased it at 60 min. ACTH response was unaffected by the simu ltaneous administration of AVP-receptor antagonists (AVP-As) y-[Phaa(1 ),D-Tyr(Et)(2),Lys(6),Arg(8)]-vasopressin or [Deamino-Pen(1),Tyr(Me)(2 ),Arg(8)]-vasopressin (20 nmol kg(-1)), but abolished by the corticotr opin-releasing hormone (CRH)-receptor antagonist alpha-helical-CRH(9-4 1) (alpha-CRH, 10 nmol kg(-1)). ET-1 evoked significant rises in the b lood levels of aldosterone and corticosterone at both 30 and 60 min. A VP-As abrogated the response at 30 min, while alpha-CRH was ineffectiv e. Both AVP-As and alpha-CRH partially reversed adrenocortical secreto ry response at 60 min. Collectively, these findings confirm that syste mically administered ET-1 stimulates rat HPA axis, and provide evidenc e that the mechanism underlying this effect may involve the sequential activation of AVP and CRH release. (C) 1998 Elsevier Science Ltd. All rights reserved.