1-DESAMINO-8-D-ARGININE VASOPRESSIN (DDAVP) IN PATIENTS WITH CONGENITAL NEPHROGENIC DIABETES-INSIPIDUS

In healthy subjects, intravenous infusion of the selective V2-vasopres sin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 n g/kg in 10 min) causes a marked increase in heart rate with a slight d ecrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenalin e (NA), clotting factor VIII (FVIII: C), von Willebrand factor (vWF: a g), and tissue-type plasminogen activator (t-PA), and a fall in the pl asma level of plasminogen activator inhibitor (PAI). None of these cha nges was observed in 3 patients with congenital nephrogenic diabetes i nsipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AV P levels in these patients were normal or slightly elevated, which mak es it unlikely that the lack of DDAVP responsiveness was caused by dow n-regulation of vasopressin V1-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, ind icating the absence of a V1-receptor defect. The responses of vWF:ag a nd t-PA to venous occlusion in the patients with NDI were similar to t hose in 5 healthy volunteers, which indicates that in NDI the endothel ial 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 plasm a levels of renin, noradrenaline, FVIII: C, vWF: ag, and t-PA through V2-receptor stimulation.