1-Desamino-8-D-Arginine Vasopressin (DDAVP) in Patients with Congenital Nephrogenic Diabetes Insipidus
| Title: | 1-Desamino-8-D-Arginine Vasopressin (DDAVP) in Patients with Congenital Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Brink, H. S.; Derkx, F.H.M.; Boomsma, F.; Brommer, E.J.P.; Schalekamp, M.A.D.H. |
| Publisher: | Netherlands Journal of Medicine |
| Date Published: | August 01, 1993 |
| Reference Number: | 126 |
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.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Intravenous administration of DDAVP causes a distinct increase in heart rate and slight decrease in diastolic blood pressure. These responses are accompanied with increases in certain blood factors associated with blood clotting and plaminogen activation.
Patients with X-linked nephrogenic diabetes insipidus (NDI) do not respond to AVP or DDAVP because their V2Rs cannot bind with either substance. Other researchers, including the authors, found that NDI patients also do not respond to the hemodynamic affects of DDAVP. That is, there is no rise in the blood clotting or other specific blood factors; there is no change in blood pressure or heart rate; there is no facial flushing. Thus it was concluded that the hemodynamic effects and the increases in the blood clotting and other blood factors were caused through V2R stimulation.
However, these results in the NDI patients could possibly have resulted from some other factors, such as:
- NDI patients could have chronically elevated AVP levels causing a downregulation of AVP.
- Perhaps both the V1R and V2Rs do not function properly in people who have NDI.
- The release of some of the measured blood factors from the cell layers lining the heart and blood levels may be defective in NDI patients.
Brink, et al., researched the effects of DDAVP on blood clotting, the dissolution of fibrin, as essential constituent of blood clots, and other hemodynamics in three patients with NDI. They designed the experiment to clarify if the lack of response to DDAVP in NDI patients was truly due to a V2R defect. They found DDAVP had no effect on blood pressure in the NDI patients, whereas it caused a slight decrease in diastolic blood pressure in the control group. The NDI group showed no increase in heart rate; the control group did. The blood factors did not increase in the NDI group; they did increase in the control group.
The possibility that the lack of effects of DDAVP in the NDI patients was due to downregulation of V1Rs was unlikely because the patients' AVP levels were hardly elevated and they showed no signs of chronic dehydration. That the one NDI patient who was infused with AVP showed an increase in blood pressure together with a fall in heart rate that rapidly returned to normal after the AVP infusion was stopped shows that his V1R was functioning. The possibility that the release of the measured blood factors from the cell lining of the heart and blood vessels might be impaired was eliminated by Bichet, et al., who showed that in NDI, plasma levels of these factors rise after adrenaline infusion.
Thus, the researchers concluded that the effects of DDAVP in normal subjects in heart rate, blood pressure and the tested blood factors are the result of V2R stimulation. And defective V2Rs are the cause of the lack of response in the NDI patients.