Ecelbarger, “Rosiglitazone activates renal sodium- and waterreabsorptive pathways and lowers blood pressure in normal rats

Synthetic agonists of the peroxisomal proliferator-activated re-ceptor subtype (PPAR-) are highly beneficial in the treatment of type II diabetes. However, they are also associated with fluid retention and edema, potentially serious side effects of un-known origin. These studies were designed to test the hypoth-esis that rosiglitazone (RGZ, PPAR- agonist) may activate sodium- and water-reabsorptive processes in the kidney, pos-sibly in response to a drop in mean arterial blood pressure (MAP), as well as directly through PPAR-. Targeted proteom-ics of the major renal sodium and water transporters and chan-nel proteins was used to identify potentially regulated sites of renal sodium and water reabsorption. RGZ (47 or 94 mg/kg diet) was fed to male, Sprague-Dawley rats (270g) for 3 days. MAP, measured by radiotelemetry, was decreased significantl