Antidiuretic action of oxytocin is associated with increased urinary excretion of aquaporin-2.

BACKGROUND The antidiuretic effect of oxytocin in humans is controversial. Urinary excretion of aquaporin-2 (AQP2) can be used as an index of the action of vasopressin on the kidney. We investigated whether exogenous oxytocin affects urinary concentration and urinary AQP2 excretion in human beings. METHODS Oxytocin was administered intravenously at a rate of 20 mU/min in 10 healthy volunteers, seven patients with central diabetes insipidus (CDI) and three patients with nephrogenic diabetes insipidus (NDI). On the next day, 2 micro g of 1-desamino-8-d-arginine vasopressin (dDAVP) was injected subcutaneously. Two-hour urine was collected before and after the administration of oxytocin and dDAVP, and urinary AQP2 was measured semi-quantitatively by western analysis. RESULTS Urine volume and free water clearance were decreased, and urine osmolality was increased by the administration of oxytocin or dDAVP in the normal volunteers and CDI patients. Urinary AQP2 excretion was increased by oxytocin infusion in the normal volunteers (from 34+/-12 to 326+/-120 densitometry unit (DU)/2 h) and in the CDI group (from 8+/-2 to 227+/-92 DU/2 h) (P<0.05), but not in the NDI group. dDAVP also had a similar but more potent effect on the urinary excretion of AQP2 in the normal and CDI groups. CONCLUSIONS Oxytocin has an antidiuretic effect and increases the urinary excretion of AQP2 in humans whose urinary concentration mechanism is preserved. These results suggest that AQP2 might have a regulatory role in the antidiuretic action of oxytocin in humans.