Renal action of a novel uricosuric diuretic, S-8666. II. Effects on Cl- and urate transport in isolated perfused rabbit renal tubules

T Shimizu, M Nakamura and M Imai

Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan.

We have studied the effect of the two enantiomeric forms of the diuretic agent, S-8666 [6,7-dichloro-5-(N,N-dimethylsulfamoyl)-2,3- dihydro-2-benzofuran carboxylic acid], on the Cl- transport across the cortical thick ascending limb of Henle's loop (CAL) and on urate transport across the proximal tubule, using the in vitro microperfusion technique of individual tubular segments isolated from the rabbit kidney. S-8666 in the lumen reduced significantly the lumen-positive voltage in CAL. The suppression of lumen-positive voltage was instantaneous, and the effects were reversible when the drug was eliminated from the perfusate. These effects were observed with the (S- )-enantiomer of S-8666 but not with the (R+)-enantiomer. S-8666 did not affect the lumen-positive voltage when it was added to the bathing fluid. The lumen to bath 36Cl flux in CAL also was reduced by addition of S-8666 to the perfusate. S-8666 in the lumen inhibited the lumen-to- bath [14C]urate flux in both proximal convoluted tubule and proximal straight tubule. It also reduced the bath-to-lumen urate flux when it was added to the bath. Enantioselectivity was not found for these inhibitory effects on urate transport of S-8666. We conclude: 1) the (S- )-enantiomer of S-8666, but not the (R+)-enantiomer, has a direct effect on the Cl- transport in the CAL, acting from the luminal side and 2) both enantiomers of S-8666 inhibit urate to transport in proximal tubules.

Volume 245, Issue 2, pp. 651-657, 05/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics