Vasopressin and catecholamine secretion during apomorphine-induced nausea mediate acute changes in haemostatic function in man

Abstract

Seven male volunteers were given apomorphine (14-20 micrograms/kg) subcutaneously on a total of ten occasions. Nausea was experienced on six occasions and on four occasions there was no effect. Venous samples were taken before injection, at peak nausea and 20 min later for assay of factor VIII coagulant activity (FVIIIC), von Willebrand factor antigen (vWFAg), the ristocetin cofactor (FVIIIRiCof), euglobulin clot lysis time (ECLT), fibrinopeptide A (FPA), FPA generation time, activated partial thromboplastin time (APTT), vasopressin (aVP) and adrenaline. During nausea plasma aVP concentrations rose from median values of 0.4 pg/ml (at time 0) to 76 pg/ml at peak nausea and fell to 32 pg/ml 20 min later. Adrenaline rose from 0.36 to 0.91 nmol/l (P less than 0.05) before falling to 0.55 nmol/l. During nausea, FVIIIC rose from 100% to 143% (P less than 0.05) and to 214% (P less than 0.05) 20 min later. FVIIIRiCof and vWFAg showed similar changes. Plasminogen activator activity (10(6)/ECLT2) rose from 23 units at time 0 to 592 units during nausea and 1135 units (P less than 0.05) after 20 min. The APTT fell from 49 s to 44 s during the study, plasma FPA levels and the FPA generation time both remained unchanged. On the four occasions nausea was not experienced, there were no changes in vasopressin and catecholamine concentrations nor in haemostatic function. During the study, plasma aVP concentrations rose to levels previously shown to influence haemostatic function. This provides further support for the view that aVP has a secondary role as a mediator of acute changes in haemostasis, and during nausea contributes with adrenaline to an abrupt change in factor VIII and fibrinolytic activator activity.

Responses of Plasma Oxytocin and Arginine Vasopressin to Nausea Induced by Apomorphine and Ipecacuanha

“…Apomorphine-induced nausea caused a marked rise in plasma AVP in normal subjects similar to that seen in other studies (Rowe et al, 1979;Baylis et al, 198,l;Sorensen & Hammer, 1985;Grant et al, 1986). We have previously demonstrated that the immunoreactive AVP released in response to this stimulus is chromatographically identical to synthetic peptide and is bioactive (Nussey et al, 1986b).…”

“…Early studies in humans and dogs showed that nausea and vomiting produced in response to several stimuli (motion sickness, ethanol, copper sulphate, apomorphine) caused a marked anti-diuresis (Andersson & Larsson, 1954;Taylor et al, 1957;Coutinho, 1969). Later studies using AVP radioimmunoassays confirmed the massive rise in plasma AVP in response to motion sickness (Eversmann et al, 1978), the dopamine (D2 receptor) agonist apomorphine (Rowe et al, 1979;Baylis et al, 1981;Sorensen & Hammer, 1985;Grant et al, 1986) and chemotherapeutic agents (Fisher et al, 1982). The role of this release of AVP in nausea and vomiting is unknown although in man therapeutic i.v.…”

Effects of a Vasopressin Antagonist in Women with Dysmenorrhea

“…Only 1 dysmenorrheic woman had markedly increased plasma concentrations of vasopressin. These might have resulted from nausea (this woman being the only one to report nausea during the experiments), as nausea is known to be a strong stimulator of vasopressin release [24]. Not only were we unable to demonstrate an effect of Atosiban on menstrual pain in dysmenorrheic women, but we also found that Atosiban had no effect on intrauterine pressure, uterine artery PI or plasma concentrations of 15-ketodihydro-PGF 2· .…”

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

“…Many treatments that produce nausea and vomiting, such as apomorphine, chemotherapy, motion, and cholecystokinin, also increase plasma vasopressin to varying extents including to levels exceeding maximal levels for anti-diuresis (Rowe et al, 1979;Fisher et al, 1982;Grant et al, 1986;Feldman et al, 1988;Miaskiewicz et al, 1989;Edwards et al, 1989;Koch et al, 1990b). Plasma vasopressin levels appear to increase slightly before or at the onset of nausea (Miaskiewicz et al, 1989;Koch et al, 1990b).…”