In the dehydrated state:

• increased plasma osmolality triggers the production of hypothalamic ADH (vasopressin).
• ADH regulates serum osmolality through the reabsorption of free water in the collecting duct (aquaporin channels), but it also causes reabsorption of urea from the collecting duct into the medullary interstitium.
• There, it contributes to the medullary osmotic gradient.