Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head‐up tilt in humans

Abstract

Of blockade of serotonin (5HT) receptors on the integrated cardiovascular and endocrine adaptations during head‐up tilt were investigated in normal men. In control experiments 50^ohead‐up tilt increased heart rate (HR), total peripheral resistance (TPR), plasma renin activity (PRA) and sympathetic activity (plasma noradrenaline; NA). A moderate increase in pituitary‐adrenal hormones (plasma ACTH, β‐END and Cortisol) was observed. After a mean tilt time of 30 ± 5min (n= 20) presyncopal symptoms associated with decreases in HR, TPR and arterial pressure occurred. At this time pituitary hormones, Cortisol, adrenomedullary (plasma adrenaline; A) as well as vagal activity (plasma pancreatic polypeptide) were markedly increased, whereas sympathetic activity (plasma NA) decreased. The 5‐HT₁₊₂ receptor antagonist methysergide did not significantly interfere with cardiovascular variables but attenuated the response of NA, prolactin (PRL), β‐endorphin (β‐END) and PRA (P < 0.02). The 5‐HT₂‐receptor antagonist ketanserin reduced the tolerated tilt time (10 ± 4 vs. 32 ± 2 min; P < 0.0003, n= 7) but had no significant effects on hormonal variables. The 5‐HT₃‐receptor antagonist ondansetron abolished the adrenomedullary response to hypotension without affecting cardiovascular tolerance or the activity of the pituitary‐adrenal axis. The results suggest that serotonergic mechanisms may be involved in the integrated cardiovascular and endocrine responses to central blood volume depletion in humans.