Distal permeability to urate and effects of benzofuran derivatives in the rat kidney

Abstract

Effects of benziodarone and benzbromarone on renal tubular permeability to urate-14C were investigated in anesthetized rats by microinjection and clearance experiments. Urate-14C and inulin-3H were injected into proximal and distal convolutions and their recovery was measured in urine collected serially. In control rats, total and direct recoveries were significantly lower after early proximal (72 and 52%, respectively) than after late proximal injections (83 and 63%), whereas distal recoveries were higher (94 and 69%). Delayed excretion (ca. 25%) did not change with site of injection. Total distal recoveries were always less than 100% (P smaller than 0.001) but increased to 98% at high loads. After proximal injections in drug-pretreated rats, total and direct recoveries increased significantly (P smaller than 0.001). Recoveries after distal injections did not change in benzbromarone-treated rats, whereas direct and delayed excretion, respectively, increased (87%) and decreased (9%) significantly (P smaller than 0.001) following benziodarone infusion. These findings demonstrate inhibition of proximal urate reabsorption by benzofuran derivatives. The results also suggest distal reabsorption of urate, presumably along the collecting ducts.