Effects of Arginine Vasopressin and 1-Desamino-8-D Arginine Vasopressin on Forearm Vasculature of Healthy Subjects and Patients with a V2 Receptor Defect
|Title:||Effects of Arginine Vasopressin and 1-Desamino-8-D Arginine Vasopressin on Forearm Vasculature of Healthy Subjects and Patients with a V2 Receptor Defect|
|Authors:||van Lieburg, Angenita; Knoers, Nine; Monnens, Leo A.H.; Smits, MD, Paul|
|Publisher:||Journal of Hypertension|
|Date Published:||December 01, 1995|
To assess which vasopressin receptor subtype mediates the vasodilation occurring in response to arginine vasopressin and 1-desamino-8-D (DD)-arginine vasopressin and whether nitric oxide is involved in these effects.
MATERIALS AND METHODS
Vasoactive effects of arginine vasopressin and DD-arginine vasopressin on forearm vasculature were studied in healthy subjects and in patients with congenital nephrogenic diabetes insipidus with a vasopressin type 2 (V2) receptor gene defect. Venous occlusion plethysmography was used to assess the forearm blood flow responses to the infusion of arginine vasopressin and its analogue into the brachial artery, in the presence and the absence of the nitric oxide synthase inhibitor L-NG-monomethyl-arginine (L-NMMA).
In healthy subjects (n = 10), DD-arginine vasopressin (0.1, 1 and 10 or 5, 10 and 20 ng/min per dl) induced a dose-related increase in forearm blood flow, but did not affect forearm blood flow in the patients with nephrogenic diabetes insipidus (N = 3). In two healthy subjects, seven increasing doses of arginine vasopressin (0.25-12 ng/min per dl) induced an initial decrease in forearm blood flow and then a gradual increase. In one of the patients, the same arginine vasopressin doses produced a persistent decrease in forearm blood flow. In the healthy subjects, infusion of L-NMMA reduced forearm blood flow significantly (n = 10). Subsequent administration of DD-arginine vasopressin during L-NMMA infusion produced a slight reduction in the forearm blood flow increase compared with DD-arginine vasopressin alone, but this was significant only for the absolute forearm blood flow increase induced by 10 ng/min per dl in all subjects. Infusion of argininue vasopressin in the presence of L-NMMA did not increase forearm blood flow significantly.
In human forearm vasculature, extrarenal V2 receptors mediate the vasodilation induced by DD-arginine vasopressin or high doses of arginine vasopressin, whereas these receptors are not necessary for arginine vasopressin-induced vasoconstriction. The DD-arginine vasopressin-induced vasodilation seems to be mediated predominantly by a mechanism other than endothelial nitric oxide release, whereas arginine vasopressin-induced vasodilation seems to involve nitric oxide release only.
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)
AVP has another effect: it can cause blood vessels to dilate. When researchers tried to find which receptor AVP binds with to exert this vasodilatory action, they found conflicting results. To see if it was the vasopressin-2 receptor that AVP bound with when it exerted a vasodilatory effect, vanLieburg, et al., measured the forearm blood flow responses of ten healthy individuals to infusions of both AVP and a synthetic AVP called 1-desamino-8-arginine vasopressin (DDAVP). The authors compared these results to the forearm blood flow responses of three patients with nephrogenic diabetes insipidus (NDI)(with proven V2R defects) similarly infused with AVP and DDAVP. The authors also wanted to know if nitric oxide was involved in AVP and DDAVP-induced vasodilatation, so they tested for this in their study as well.
The authors found that DDAVP induced a dose-related increase in forearm blood flow in seven of the healthy subjects they tested, but not in the three NDI patients. When the authors administered increasing doses of AVP to two healthy subjects, they showed a gradual increase in forearm blood flow, but the NDI patient they tested actually showed a decrease in forearm blood flow.
To test if nitric oxide was involved in the blood vessel dilation process, the authors administered a nitric oxide inhibitor at certain points during the test so that at different times nitric oxide would be present during the test and at other times it would be absent. When DDAVP was administered to ten healthy subjects in the absence of nitric oxide, there was a partial reduction in the forearm blood flow increase DDAVP had previously induced. When AVP was administered in the absence of nitric oxide, it produced no significant increase in forearm blood flow.
The reason the authors tested healthy subjects against subjects with NDI is because NDI is often (and in these three subjects, definitely) associated with defects in the V2Rs that prevent it from binding with AVP. As a result, NDI patients cannot concentrate urine, nor when exposed to DDAVP do they show vasodilatory, coagulation or other blood clotting responses to DDAVP that people without NDI show.
The authors' research proved several things:
- The absence of vasodilatation during administration of DDAVP and high doses of AVP in NDI patients proves that both effects are accomplished through the aid of V2R.
- The high selectivity DDAVP shown for V2Rs in the kidney is also shown for V2Rs outside the kidney.
- The absence of the NDI patients' V2R response to DDAVP is a direct consequence of defects of the V2R that are located outside the kidney, and not a consequence of the defective V2Rs inside the kidney which cause their NDI.
The findings on the necessity of the presence of nitric oxide are less clear, though still significant. When nitric oxide was absent, DDAVP-induced vasodilatation was hardly reduced, if at all. Whereas when nitric oxide was absent, AVP-induced vasodilatation was almost completely inhibited. This led the authors to conclude that DDAVP-induced vasodilatation seems to be mediated predominantly by a mechanism other than the release of nitric oxide, whereas AVP-induced vasodilatation seems to involve nitric oxide release only.