Oxytocin as an antidiuretic hormone. I. Concentration dependence of action

C. L. Chou, S. R. DiGiovanni, R. Mejia, S. Nielsen and M. A. Knepper Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Circulating concentrations of oxytocin increase to 10-40 pM in rats in response to osmotic stimuli, suggesting that oxytocin could play a role in regulation of water balance. The present studies tested whether oxytocin at such concentrations increases osmotic water permeability (Pf) in isolated perfused terminal inner medullary collecting ducts (IMCD). In IMCD segments from Sprague-Dawley rats, 20 pM oxytocin added to the peritubular bath caused a two- to threefold increase in Pf, whereas 200 pM oxytocin increased Pf by five- to sixfold (n = 8, P < 0.01). IMCD from Brattleboro rats, which manifest central diabetes insipidus, exhibited a 2.8-fold increase in Pf in response to 20 pM oxytocin and a 4.7-fold increase in response to 200 pM oxytocin. However, in Brattleboro rats, the response to 20 pM oxytocin was dependent on prior water restriction of the rats. Immunoblotting showed no change in the expression of the aquaporin-CD water channel in Brattleboro rats in response to water restriction. Nevertheless, immunofluorescence studies of inner medullary tissue from Brattleboro rats revealed a marked redistribution of the aquaporin-CD water channels to a predominantly apical and subapical localization in IMCD cells in response to water restriction, similar to the redistribution seen in response to vasopressin. Mathematical modeling studies revealed that the measured increase in Pf in response to oxytocin is sufficient to generate a concentrated urine. We conclude that oxytocin can function physiologically as an antidiuretic hormone, mimicking the short-term action of vasopressin on water permeability, albeit with somewhat lower potency.