AJP - Endocrinology and Metabolism, Vol 270, Issue 3 E513-E521, Copyright © 1996 by American Physiological Society
Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin
J. A. Saydoff, P. A. Rittenhouse, M. Carnes, J. Armstrong, L. D. Van De Kar and M. S. Brownfield
Department of Comparative Biosciences, Schools of Veterinary Medicine, University of Wisconsin, Madison 53706, USA.
Central serotonin (5-HT) and angiotensin (ANG II) stimulate arginine
vasopressin (AVP), 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 the angiotensin-converting enzyme inhibitor enalapril
before injection of the 5-HT releaser/uptake inhibitor d-fenfluramine.
Fenfluramine (2 mg/kg ip) stimulated AVP, OT, corticosterone, and prolactin
(PRL) secretion (P<0.01). Enalapril (60 mg/l in drinking water for 4
days and 10 mg/kg ip 2 h before the rats were killed) inhibited only the
AVP response (P<0.01) to d-fenfluramine. In the second study, the effect
of intracerebroventricular injection of the 5-HT2A/2C antagonist LY-53857
(10 microgram), or the ANG II AT1 antagonist DuP-753 (10 microgram), on
intracerebroventricular 5-HT (10 microgram)-stimulated AVP, OT, ACTH, PRL,
renin secretion, mean arterial pressure (MAP) and heart rate (HR) was
tested. LY-53857 inhibited the AVP, OT, and ACTH responses to 5-HT
(P<0.01), whereas DuP-753 inhibited only the AVP response (P<0.01).
Intraventricular injection of 5-HT increased MAP and decreased HR. The MAP
response was not affected by LY-53857 or DuP-753, and at no time did MAP
decline below starting levels. The decreased HR was inhibited by LY-53857
but not by DuP-753. These results demonstrate that 5-HT-induced AVP
secretion is mediated selectively via brain angiotensinergic mechanisms by
way of the AT1 receptor.
