1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus
Brink, H.S.; Derkx, F.H.; Boomsma, F.; Brommer, E.J.; Schalekamp, M.A.
Netherlands Journal of Medicine 43(1-2): 5-12
1993
ISSN/ISBN: 0300-2977 PMID: 8232694 Document Number: 418475
In healthy subjects, intravenous infusion of the selective V-2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. The haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V-2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V-1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal indicating the absence of a V-1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V-2-receptor stimulation.