GI262570, a Peroxisome Proliferator-Activated Receptor Agonist, Changes Electrolytes and Water Reabsorption from the Distal Nephron in Rats

Peroxisome proliferator-activated receptor- (PPAR) agonists have been shown to have significant therapeutic benefits such as desirable glycemic control in type 2 diabetic patients; how-ever, these agents may cause fluid retention in susceptible individuals. Since PPAR is expressed selectively in distal nephron epithelium, we studied the mechanism of PPAR ag-onist-induced fluid retention using male Sprague-Dawley rats treated with either vehicle or GI262570 (farglitazar), a potent PPAR agonist. GI262570 (20 mg/kg/day) induced a plasma volume expansion. The plasma volume expansion was accom-panied by a small but significant decrease in plasma potassium concentration. Small but significant increases in plasma so-dium and chloride concentrations were also observed. These changes in serum electrolytes suggested an activation of th