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

Abstract

To examine the role of aquaporin-1 (AQP1) in near-isosmolar fluid reabsorption in the proximal tubule, we compared osmolalities in micropuncture samples of late proximal tubular fluid and plasma in wild-type (+/+) and AQP1-knockout (−/−) mice. Compared with matched wild-type mice, the −/− animals produce a relatively hypotonic urine (607 ± 42 vs. 1,856 ± 101 mosmol/kgH2O) and have a higher plasma osmolality under micropuncture conditions (346 ± 11 vs. 318 ± 5 mosmol/kgH2O; 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/kgH2O. Late proximal tubular fluid osmolalities were 309 ± 5 (+/+, n= 21), 309 ± 4 (−/−, n = 24), and 284 ± 3 mosmol/kgH2O (hydrated −/−, n = 19). Tubular fluid chloride concentration averaged 152 ± 1 (+/+), 154 ± 1 (−/−), and 140 ± 1 mM (hydrated −/−). Transtubular osmotic gradients in untreated and hydrated AQP1 −/− mice were 39 ± 4 ( n = 25) and 39 ± 3 mosmol/kgH2O ( n = 19), values significantly higher than in +/+ mice (12 ± 2 mosmol/kgH2O; n = 24; both P < 0.001). AQP1 deficiency in mice generates marked luminal hypotonicity in proximal tubules, resulting from the retrieval of a hypertonic absorbate and indicating that near-isosmolar fluid absorption requires functional AQP1.