Am J Physiol Cell Physiol AJP: Cell Physiology
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Am J Physiol Cell Physiol 276: C76-C81, 1999;
0363-6143/99 $5.00
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Vol. 276, Issue 1, C76-C81, January 1999

Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice

Baoxue Yang1, Hans G. Folkesson2, Jian Yang1, Michael A. Matthay1, Tonghui Ma1, and A. S. Verkman1

1 Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521; and 2 Department of Animal Physiology, Lund University, Lund, Sweden

Aquaporin-1 (AQP1) water channels are expressed widely in epithelia and capillary endothelia involved in fluid transport. To test whether AQP1 facilitates water movement from capillaries into the peritoneal cavity, osmotically induced water transport rates were compared in AQP1 knockout [(-/-)], heterozygous [(+/-)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8. Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma. For measurement of water transport, 2 ml of saline containing 300 mM sucrose (600 mosM) were infused rapidly into the peritoneal cavity via a catheter. Serial fluid samples (50 µl) were withdrawn over 60 min, with albumin as a volume marker. The albumin dilution data showed significantly decreased initial volume influx in AQP1 (-/-) mice: 101 ± 8, 107 ± 5, and 42 ± 4 (SE) µl/min in (+/+), (+/-), and (-/-) mice, respectively [n = 6-10, P < 0.001, (-/-) vs. others]. Volume influx for AQP4 knockout mice was 100 ± 8 µl/min. In the absence of an osmotic gradient, 3H2O uptake [half time = 2.3 and 2.2 min in (+/+) and (-/-) mice, respectively], [14C]urea uptake [half time = 7.9 and 7.7 min in (+/+) and (-/-) mice, respectively], and spontaneous isosmolar fluid absorption from the peritoneal cavity [0.47 ± 0.05 and 0.46 ± 0.04 ml/h in (+/+) and (-/-) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis.

peritoneum; peritoneal dialysis; aquaporins; transgenic mice; water pores


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