ROLE OF RENAL AQUAPORINS IN ESCAPE FROM VASOPRESSIN-INDUCED ANTIDIURESIS IN RAT

The purpose of this study was to investigate whether escape from vasop ressin-induced antidiuresis is associated with altered regulation of a ny of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rat s were divided into two groups: control (continued dDAVP) and water-lo aded (continued dDAVP plus a daily oral water load). A significant inc rease in urine volume in the water-loaded rats was observed by the sec ond day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal a quaporin-2 protein (measured by semiquantitative immunoblotting), whic h began at day 2 and fell to 17% of control levels by day 3. In contra st, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was a ccompanied by a concomitant suppression of whole kidney aquaporin-2 mR NA levels. Immunocytochemical localization and differential centrifuga tion studies demonstrated that trafficking of aquaporin-2 to the plasm a membrane remained intact during vasopressin escape. The results sugg est that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin- 2 water channel expression in the renal collecting duct.