Aquaporin-1 plays an essential role in water permeability and ultrafiltration during peritoneal dialysis.
The water channel aquaporin-1 (AQP1) is considered as the molecular counterpart of the ultrasmall pore predicted by the three-pore model of fluid transport across the peritoneal membrane. However, the definitive proof of the implication of AQP1 in solute-free water transport, sodium sieving, and ultrafiltration (UF) during peritoneal dialysis (PD) is lacking, and the effects of its deletion on the structure of the membrane are unknown. Using real-time reverse transcriptase-polymerase chain reaction and immunogold electron microscopy, we showed that AQP1 is the most abundant member of the AQP gene family expressed in the mouse peritoneum, and the only one located in the capillary endothelium. Transport studies during a 2-h dwell demonstrated that, in comparison with Aqp1(+/+) littermates, Aqp1(-/-) mice had no sodium sieving; an approximately 70% decrease in the initial, solute-free UF; and an approximately 50% decrease in cumulative UF. These modifications occurred despite unchanged osmotic gradient and transport of small solutes in the Aqp1(-/-) mice. Heterozygous Aqp1(+/-) mice showed intermediate values in sodium sieving and initial UF, whereas cumulative UF was similar to Aqp1(+/+) mice. The deletion of AQP1 had no effect on the expression of other AQPs and on the density, structure, or diameter of peritoneal capillaries. These data provide direct evidence for the role of AQP1 during PD. They validate essential predictions of the three-pore model: (i) the ultrasmall pores account for the sodium sieving, and (ii) they mediate 50% of UF during a hypertonic dwell.
Ni
J
J
Division of Nephrology and Department of Pathology, UCL Medical School, Brussels, Belgium.
Verbavatz
J-M
JM
Rippe
A
A
Boisdé
I
I
Moulin
P
P
Rippe
B
B
Verkman
A S
AS
Devuyst
O
O
D000818:Animals; D051398:Aquaporin 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001692:Biological Transport; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001834:Body Water / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D015870:Gene Expression; D017583:Hemodiafiltration; D051379:Mice; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism* / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism
D015415:Biomarkers; D051398:Aquaporin 1; D012964:Sodium