Luminal hypotonicity in proximal tubules of aquaporin-1-knockout mice.
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/kgH(2)O) and have a higher plasma osmolality under micropuncture conditions (346 +/- 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), 309 +/- 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 untreated and hydrated AQP1 -/- mice were 39 +/- 4 (n = 25) and 39 +/- 3 mosmol/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 retrieval of a hypertonic absorbate and indicating that near-isosmolar fluid absorption requires functional AQP1.
Vallon
V
V
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Verkman
A S
AS
Schnermann
J
J
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D005260:Female; D006982:Hypertonic Solutions; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration
C496021:Aqp1 protein, mouse; D020346:Aquaporins; D006982:Hypertonic Solutions; D051398:Aquaporin 1