Effects of Chronic Rosiglitazone Treatment on Renal Handling of Salt and Water in Rats With Volume-Overload Congestive Heart Failure

Background—The side effects of fluid retention and edema of the thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor-γ agonists limit their use in patients with congestive heart failure (CHF). The present study aims to explore whether chronic treatment with the TZD compound rosiglitazone (RGZ) is associated with worsening of salt and water retention in male Sprague-Dawley rats with aorto-caval fistula, an experimental model of volume-overload CHF. Methods and Results—The effects of oral RGZ (30 mg/kg per day for 4 weeks) in CHF rats on plasma volume, cumulative sodium excretion, renal expression of Na+ channels and transporters, and selected biomarkers of CHF were compared with those in CHF rats and sham-operated control rats treated with vehicle only (n=7 to 10). Additionally, the response to acute saline loading (3.5% of body weight) was evaluated after 2 weeks of treatment by renal clearance methodology. Chronic RGZ treatment caused no further increase in plasma volume compared w...