1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus.
In healthy subjects, intravenous infusion of the selective V2-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. These 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 V2-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 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, indicating the absence of a V1-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 V2-receptor stimulation.
Brink
H S
HS
Department of Internal Medicine I, Erasmus University, Rotterdam, Netherlands.
Derkx
F H
FH
Boomsma
F
F
Brommer
E J
EJ
Schalekamp
M A
MA
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D003919:Diabetes Insipidus / Q000097:blood / Q000151:congenital* / Q000188:drug therapy* / Q000503:physiopathology; D005169:Factor VIII / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood; D015849:Plasminogen Inactivators / Q000097:blood; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics; D012083:Renin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D015849:Plasminogen Inactivators; D017483:Receptors, Vasopressin; D014841:von Willebrand Factor; D005169:Factor VIII; D010959:Tissue Plasminogen Activator; D012083:Renin; D003894:Deamino Arginine Vasopressin; D009638:Norepinephrine