Aldosterone Regulates Vasopressin Escape through Changes in Water and Urea Transporters.

Vasopressin escape is a process that prevents the continuous decrease in serum sodium even under conditions of sustained high vasopressin. Previous reports suggest that this process is regulated by aldosterone but the mechanism is not fully defined. In this study, aldosterone synthase (Cyp11b2) knockout and wild-type mice were implanted with 14-day osmotic mini-pumps delivering 5 ng/h dDAVP (desmopressin, type 2 vasopressin receptor agonist) to promote distal nephron water reabsorption. Urine osmolality was measured before and then daily (24-h urine collections) throughout the experiment. After 4 days of increased urine osmolality, mice were given a gel diet to force additional fluid consumption. Urine osmolality of the wild type mice was significantly lower (successful escape) than that of aldosterone synthase knockout mice. Protein analysis showed that both AQP2 and UT-A1 protein abundances were higher in the aldosterone synthase knockout than wild-type mice at the end of the escape period. To confirm the findings from the aldosterone synthase knockout mice, the mineralocorticoid receptor blocker spironolactone (20mg/kg/day, s.c.) or vehicle was given to rats that were receiving vasopressin by mini-pump in a comparable vasopressin escape protocol to the mice. The spironolactone-treated rats displayed a higher urine osmolality and lower serum sodium level versus untreated escaping rats. Phosphoserine 256-AQP2 (PS256-AQP2) was significantly increased in the spironolactone-treated rats. Our results indicate that: vasopressin escape is prevented if aldosterone or its receptor are not available; and increased abundance of AQP2 or UT-A1, or PS256-AQP2, contributes to deficient vasopressin escape in the absence of aldosterone.