Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin.
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.
Saydoff
J A
JA
Department of Comparative Biosciences, Schools of Veterinary Medicine, University of Wisconsin, Madison 53706, USA.
Rittenhouse
P A
PA
Carnes
M
M
Armstrong
J
J
Van De Kar
L D
LD
Brownfield
M S
MS
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology*; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D010121:Oxytocin / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
D000324:Adrenocorticotropic Hormone; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001127:Arginine Vasopressin; D001713:Biphenyl Compounds; D003345:Corticosterone; D004656:Enalapril; D004873:Ergolines; D005277:Fenfluramine; D007093:Imidazoles; D019808:Losartan; D010121:Oxytocin; D011388:Prolactin; D012083:Renin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013777:Tetrazoles; C032663:LY 53857