title: Neuroendocrine mechanisms during reversible hypovolaemic shock in humans with emphasis on the histaminergic and serotonergic system.
abstract: In humans, the head-up tilted position results in central hypovolaemia which mimicks haemorrhage and is associated with cardiovascular changes that can be divided into two stages. 1) One stage with increase in HR and vascular resistance and a slight increase in MAP. 2) Another stage with decrease in HR, vascular resistance and MAP and appearance of presyncopal symptoms (hypovolaemic shock). The first stage is "sympathoexcitatory" as plasma NA originating from postganglionic vasoconstrictory sympathetic neurons increase. Limb vascular resistance contributes to the increase in TPR at this time. The second stage is "sympathoinhibitory" in nature as plasma NA slightly decreases, or remains unchanged, while plasma A, originating from the adrenal medulla, raises. This pattern is a reflection of a differentiated sympathetic response as an increase in the activity of the nerves innervating the adrenals and decrease in renal sympathetic nerves has been reported by others. There is a decrease in limb as well as total vascular resistance. The secretion of potent vasoactive peptides may contribute to the circulatory changes taken place during head-up tilt. The head-up tilted position is associated with central hypovolaemia which is reliably monitored by electrical impedance. There is a close relation between the increase in thoracic electrical impedance and the decrease in plasma ANP which is regulated by atrial stretch. Also, from recording of technetium labeled red blood cells and measurements of haematocrite the decrease in CBV is reflected by thoracic electrical impedance. In contrast, CVP reflects changes in CBV during the initial head-up tilt only, whereafter CVP usually is unchanged or may even increase. After the initial head-up tilt the decrease in the CBV is caused by further reduction in plasma volume as shown by increase in haematocrite and unchanged distribution of labeled red blood cells. This mechanism is reflected by application of regional electrical impedance measurements at a low and high frequency current. The low frequency current, passing extracellular fluid only, changing more than the high frequency current that passes extra as well as intracellular fluid. Central hypovolaemia was found to stimulate the pituitary-adrenal axis, and the development of hypotension strongly increases plasma ACTH, beta-END, cortisol and PRL. Blocking histaminergic receptors did not change the pituitary-adrenal response to central hypovolaemia, while the sympathoadrenal response was affected by histaminergic receptor blockade. The H2-receptor antagonist cimetidine inhibited plasma A, while the H1-receptor antagonist mepyramine attenuated plasma NA and reduced cardiovascular tolerance, and also induced some sedation. A possible effect of sedation and anxiolysis was investigated by administration of the GABAergic drug diazepam. This drug did not change the cardiovascular response to head-up tilt, but reduced the increase in plasma cortisol. This indicates that the appearance of presyncopal symptoms is not related to "stress" but associated with the cardiovascular effects of central hypovolaemia. Another endogenous substance, serotonin (5-HT), may be also involved in cardiovascular as well as endocrine regulation. We investigated the effect of blocking three main receptors on the development and effects of hypovolaemic shock. Methysergide (5-Ht1+2-receptor antagonist) attenuated plasma NA, beta-END, PRL and PRA during tilt with a slight reduction of cardiovascular tolerance. The 5-HT2-receptor antagonist ketanserin reduced cardiovascular tolerance without significant effects on the hormonal responses. The 5-HT3-receptor antagonist ondansetron inhibited the plasma CGRP and adrenalin response to central hypovolaemia without influencing cardiovascular tolerance. It is concluded that the head-up tilted model in humans can be applied to study cardiovascular and endocrine mechanisms until the development of hypovolaemic shock.(ABSTRACT TRUNCATED)
authors.affiliation: Department of Medical Physiology, Panum Institute, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Matzen
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002560:Cerebrovascular Circulation; D018475:Head-Down Tilt; D006632:Histamine / Q000502:physiology*; D006801:Humans; D009490:Neurosecretory Systems / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012769:Shock / Q000503:physiopathology*
chemical_list: D018377:Neurotransmitter Agents; D012701:Serotonin; D006632:Histamine