Fluid Retention Caused by Rosiglitazone Is Related to Increases in AQP2 and ENaC Membrane Expression.

Peroxisome proliferator activated receptor- (PPAR) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. The decreased phosphorylation of PPAR due to rosiglitazone (ROS) is the main reason for the increased insulin sensitivity caused by this antidiabetic drug. However, there is no clear evidence whether the nuclear translocation of p-PPAR stimulated by ROS is related to fluid retention. It is also unclear whether the translocation of p-PPAR is associated with the change of aquaporin-2 (AQP2) and epithelial sodium channel subunit (ENaC) in membranes, cytoplasm, and nucleus. Our experiments indicate that ROS significantly downregulates nuclear p-PPAR and increases membrane AQP2 and ENaC; however, SR1664 (a nonagonist PPAR ligand) reduces p-PPAR and has no effect on AQP2 and ENaC. Therefore, we conclude that in vitro the fluid retention caused by ROS is associated with the increases in membrane ENaC and AQP2 but has little relevance to the phosphorylation of PPAR.