Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head-up tilt in humans.
Effects of blockade of serotonin (5-HT) receptors on the integrated cardiovascular and endocrine adaptations during head-up tilt were investigated in normal men. In control experiments 50 degrees head-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, beta-END and cortisol) was observed. After a mean tilt time of 30 +/- 5 min (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), beta-endorphin (beta-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.
Matzen
S
S
Department of Medical Physiology, Panum Institute, Copenhagen, Denmark.
Secher
N H
NH
Knigge
U
U
Pawelczyk
J
J
Perko
G
G
Iversen
H
H
Bach
F W
FW
Warberg
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood*; D017294:Ondansetron / Q000494:pharmacology*; D011187:Posture; D011388:Prolactin / Q000097:blood; D012016:Reference Values; D012083:Renin / Q000097:blood* / Q000187:drug effects; D012702:Serotonin Antagonists; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D001615:beta-Endorphin / Q000097:blood
D006728:Hormones; D012702:Serotonin Antagonists; D017294:Ondansetron; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007650:Ketanserin; D012083:Renin; D006854:Hydrocortisone; D009638:Norepinephrine; D008784:Methysergide