Neuroendocrine and cardiovascular activation by serotonin:
selective mediation by brain angiotensin on vasopressin
secretion.
Saydoff, J. A., P. A. Rittenhouse, M. Carnes, J. Armstrong, L. D. Van
De Kar, and M. S. Brownfield.
Neurosciences Training Program, and the Department of Comparative
Biosciences, School of Veterinary Medicine, University of Wisconsin,
Madison, WI 53706, Radioimmunoassay and Radionuclide Laboratory,
School of Veterinary Medicine, University of Wisconsin, Madison, WI
53706, Department of Medicine, School of Medicine, University of
Wisconsin, and the Geriatric Research and Education Clinical Center
Middleton Veterans Administration Hospital, Madison, WI 53706,
Department of Pharmacology and Experimental Therapeutics, Loyola
University Stritch School of Medicine, Maywood, IL 60153
APStracts 2:0217E, 1995.
Central serotonin (5-HT) and angiotensin (ANG II) stimulate
vasopressin (VP), oxytocin (OT), and adrenocorticotropin (ACTH)
secretion and increase blood pressure. Studies were conducted in
conscious rats to determine whether neuroendocrine activation by 5-HT
requires a brain angiotensinergic intermediate pathway. In the first
study, ANG II formation was inhibited by angiotensin converting
enzyme (ACE) inhibitor enalapril before injecting the 5-HT
releaser/uptake inhibitor d-fenfluramine. Fenfluramine (2 mg/kg, IP)
stimulated VP, OT, CORT, and PRL secretion (P<0.01). Enalapril
(60 mg/L in drinking water for 4 days and 10 mg/kg IP two hours
before killing) inhibited only the VP response (P<0.01) to d
-fenfluramine. In the second study, the effect of ICV injection of the
5-HT2A\2C antagonist LY53857 (10 mg), or the angiotensin II AT1
antagonist DuP753 (10 mg) on ICV 5-HT (10 mg)-stimulated VP, OT,
ACTH, PRL, and renin secretion, and mean arterial pressure (MAP) and
heart rate (HR) was tested. LY53857 inhibited the VP, OT, and ACTH
responses to 5-HT (P<0.01) while DuP753 inhibited only the VP
response (P<0.01). ICV injection of 5-HT increased MAP and
decreased HR.. The MAP response was not affected by LY53857 or DuP
753 and at no time did MAP decline below starting levels. The
decreased HR was inhibited by LY53857, but not by DuP753. These
results demonstrate that 5-HT induced VP secretion is mediated
selectively via brain angiotensinergic mechanisms by way of the AT1
receptor.
Received 15 May 1995; accepted in final form 17 October 1995.
APS Manuscript Number E220-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95