title: Novel Endothelial Cell-Specific AQP1 Knockout Mice Confirm the Crucial Role of Endothelial AQP1 in Ultrafiltration during Peritoneal Dialysis.
abstract: The water channel aquaporin-1 (AQP1) mediates about 50% ultrafiltration during a 2-hour hypertonic dwell in global AQP1 knockout (AQP1-/-) mice. Although AQP1 is widely expressed in various cell types including mesothelial cells, the ultrafiltration has been assumed to be mediated via endothelial AQP1 of the peritoneum. The partial embryonic lethality and reduced body weight in AQP1-/- mice may reflect potential confounding phenotypic effects evoked by ubiquitous AQP1 deletion, which may interfere with functional analysis of endothelial AQP1. Using a Cre/loxP approach, we generated and characterised endothelial cell- and time-specific AQP1 knockout (AQP1fl/fl; Cdh5-Cre+) mice. Compared to controls, AQP1fl/fl; Cdh5-Cre+ mice showed no difference in an initial clinical and biological analysis at baseline, including body weight and survival. During a 1-hour 3.86% mini-peritoneal equilibration test (mini-PET), AQP1fl/fl; Cdh5-Cre+ mice exhibited strongly decreased indices for AQP1-related transcellular water transport (43.0% in net ultrafiltration, 93.0% in sodium sieving and 57.9% in free water transport) compared to controls. The transport rates for small solutes of urea and glucose were not significantly altered. Our data provide the first direct experimental evidence for the functional relevance of endothelial AQP1 to the fluid transport in peritoneal dialysis and thereby further validate essential predictions of the three-pore model of peritoneal transport.
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
authors.affiliation: Transgenic Service, German Cancer Research Centre, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: van der Hoeven
authors.affiliation: Department of Endocrinology and Metabolism, University of Heidelberg, Heidelberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Katus
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kälble
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Zitron
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.|Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
mesh_terms: D000483:Alleles; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D001692:Biological Transport; D002469:Cell Separation; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D018390:Gene Targeting; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010530:Peritoneal Dialysis; D015203:Reproducibility of Results; D014462:Ultrafiltration; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D051398:Aquaporin 1