Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans.
In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n = 6) and in patients with central (C; n = 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n = 3) or AVPR2 (n = 10). dDAVP was infused intravenously (0.3 microg/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. The magnitude of the fall in sodium excretion correlated with the rise in urine osmolality and the fall in urine output but not with the simultaneously observed fall in mean BP. These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor-dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined.
Bankir
Lise
L
INSERM Unité 367, Institut du Fer à Moulin, 17 Rue du Fer à Moulin, 75005 Paris, France. bankir@fer-a-moulin.inserm.fr
Fernandes
Sandrine
S
Bardoux
Pascale
P
Bouby
Nadine
N
Bichet
Daniel G
DG
D000293:Adolescent; D000328:Adult; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics; D002648:Child; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D003919:Diabetes Insipidus / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012076:Renal Agents / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
C496023:AQP2 protein, human; D051399:Aquaporin 2; D020346:Aquaporins; D017483:Receptors, Vasopressin; D012076:Renal Agents; D015222:Sodium Channels; D012964:Sodium; D003894:Deamino Arginine Vasopressin