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

TY - JOUR

T1 - Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head-up tilt in humans

AU - Matzen, S

AU - Secher, N H

AU - Knigge, U

AU - Pawelczyk, J

AU - Perko, G

AU - Iversen, H

AU - Bach, F W

AU - Warberg, J

AU - Iversen, Helle Klingenberg

PY - 1993/10

Y1 - 1993/10

N2 - 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.

AB - 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.

KW - Adrenocorticotropic Hormone

KW - Blood Pressure

KW - Heart Rate

KW - Hemodynamics

KW - Hormones

KW - Humans

KW - Hydrocortisone

KW - Ketanserin

KW - Male

KW - Methysergide

KW - Norepinephrine

KW - Ondansetron

KW - Posture

KW - Prolactin

KW - Reference Values

KW - Renin

KW - Serotonin Antagonists

KW - Vagus Nerve

KW - Vascular Resistance

KW - beta-Endorphin

U2 - 10.1111/j.1748-1716.1993.tb09609.x

DO - 10.1111/j.1748-1716.1993.tb09609.x

M3 - Journal article

C2 - 8266806

SN - 0001-6772

VL - 149

SP - 163

EP - 176

JO - Acta Physiologica Scandinavica

JF - Acta Physiologica Scandinavica

IS - 2

ER -