Corticosteroids induce expression of aquaporin-1 and increase transcellular water transport in rat peritoneum.
The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore responsible for transcellular water permeability during peritoneal dialysis (PD). This water permeability accounts for up to 50% of ultrafiltration (UF) during a hypertonic dwell, and its loss can be a major clinical problem for PD patients. By analogy with the lung, the hypothesis was tested that corticosteroids may increase AQP1 expression in the peritoneal membrane (PM) and improve water permeability and UF in rats. First, the expression and distribution of the glucocorticoid receptor (GR) in the PM and capillary endothelium was documented. Time-course and dose-response analyses showed that a daily IM injection of dexamethasone (1 or 4 mg/kg) for 5 d induced an approximately twofold increase in the expression of AQP1 at the mRNA and protein levels. The GR antagonist RU-486 completely inhibited the dexamethasone effect. The functional counterpart of the increased AQP1 expression was a significant increase in sodium sieving and net UF across the PM, contrasting with a lack of effect on the osmotic gradient and permeability for small solutes. The latter observation reflected the lack of effect of corticosteroids on nitric oxide synthase (NOS) activity and endothelial NOS isoform expression in the PM. In conclusion, corticosteroids induce AQP1 expression in the capillary endothelium of the PM, which is reflected by increased transcellular water permeability and UF. These data emphasize the critical role of AQP1 during PD and suggest that pharmacologic regulation of AQP1 may provide a target for manipulating water permeability across the PM.
Stoenoiu
Maria S
MS
Division of Nephrology and ENDO Unit, Université Catholique de Louvain Medical School, Brussels, Belgium.
Ni
Jie
J
Verkaeren
Charlotte
C
Debaix
Huguette
H
Jonas
Jean-Christophe
JC
Lameire
Norbert
N
Verbavatz
Jean-Marc
JM
Devuyst
Olivier
O
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004727:Endothelium / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009995:Osmosis / Q000187:drug effects; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
C496022:Aqp1 protein, rat; D020346:Aquaporins; D005938:Glucocorticoids; D014867:Water; D051398:Aquaporin 1; D003907:Dexamethasone; D019001:Nitric Oxide Synthase