Luminal hypotonicity in proximal tubules of aquaporin-1-knockout mice

To examine the role of aquaporin-1 (AQP1) in near-isosmolar fluid reabsorpt ion in the proximal tubule, we compared osmolalities in micropuncture sampl es of late proximal tubular fluid and plasma in wild-type (+/+) and AQP1-kn ockout (-/-) mice. Compared with matched wild-type mice, the -/- animals pr oduce a relatively hypotonic urine (607 +/- 42 vs. 1,856 +/- 101 mosmol/kgH (2)O) and have a higher plasma osmolality under micropuncture conditions (3 46 +/- 11 vs. 318 +/- 5 mosmol/kgH(2)O; P < 0.05). Measurements of tubular fluid osmolality were done in three groups of mice, +/+, -/-, and hydrated -/- mice in which plasma osmolality was reduced to 323 +/- 1 mosmol/kgH(2)O . Late proximal tubular fluid osmolalities were 309 +/- 5 (+/+, n = 21), 30 9 +/- 4 (-/-, n = 24), and 284 +/- 3 mosmol/kgH(2)O (hydrated -/-, n = 19). Tubular fluid chloride concentration averaged 152 +/- 1 (+/+), 154 +/- 1 ( -/-), and 140 +/- 1 mM (hydrated -/-). Transtubular osmotic gradients in un treated and hydrated AQP1 -/- mice were 39 +/- 4 (n = 25) and 39 +/- 3 mosm ol/kgH(2)O (n = 19), values significantly higher than in +/+ mice (12 +/- 2 mosmol/kgH(2)O; n = 24; both P < 0.001). AQP1 deficiency in mice generates marked luminal hypotonicity in proximal tubules, resulting from the retrie val of a hypertonic absorbate and indicating that near-isosmolar fluid abso rption requires functional AQP1.