NEUROENDOCRINE AND CARDIOVASCULAR EFFECTS OF SEROTONIN - SELECTIVE ROLE OF BRAIN ANGIOTENSIN ON VASOPRESSIN

Central serotonin (5-HT) and angiotensin (ANG II) stimulate arginine v asopressin (AVP), oxytocin (OT), and adrenocorticotropin (ACTH) secret ion and increase blood pressure. Studies were conducted in conscious r ats to determine whether neuroendocrine activation by 5-HT requires a brain angiotensinergic intermediate pathway. In the first study, ANG L I formation was inhibited by the angiotensin-converting enzyme inhibit or enalapril before injection of the 5-HT releaser/uptake inhibitor d- fenfluramine. Fenfluramine (2 mg/kg ip) stimulated AVP, OT, corticoste rone, 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 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 mu g), or the ANG II AT(1) antagonist DuP-753 (10 mu g), on intracerebroventricular 5-HT (10 mu g)stimulate d AVP, OT, ACTH, PRL, renin secretion, mean arterial pressure (MAP) an d 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 decrea sed HR was inhibited by LY-53857 but not by DuP-753. These results dem onstrate that 5-HT-induced AVP secretion is mediated selectively via b rain angiotensinergic mechanisms by way of the AT(1) receptor.