EFFECT OF DIURETICS ON SODIUM AND CHLORIDE PERMEABILITY IN THE RAT PAPILLARY COLLECTING DUCT

While in vivo data suggests that diuretics such as furosemide and hydr ochlorothiazide alter inner medulla collecting duct (IMCD) cell electr olyte transport, this has not been confirmed by in vivo studies nor ha ve the mechanisms been evaluated. This study evaluated the direct effe ct of these diuretics as well as amiloride on sodium and chloride unid irectional permeability in the isolated perfused rat IMCD. In the abse nce of diuretics, the permeability of sodium was lower than that of ch loride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 mu m/s), although bo th were relatively impermeable when compared to water. Furosemide (10( -4)) and hydrochlorothiazide (10(-3)) both increased the diffusional p ermeability of chloride by approximately 30%(0.80 +/- 0.06 to 1.04 +/- 0.09 mu m/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 mu m/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhi bition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuret ic AVP concentration did not alter sodium or chloride permeability. Ho wever, increasing the lumen and bath sodium chloride concentration fro m 150 to 300 and 600 mM significantly increased both sodium and partic ularly chloride conductance. In contrast, amiloride (10-4) significant ly reduced both sodium and chloride permeability. These studies suppor t a direct effect of furosemide and hydrochlorothiazide on the IMCD an d suggest that their in vivo effect is primarily mediated by facilitat ing the passive movement of chloride into the lumen via a favourable e lectrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mech anisms separate to that of the sulphonamide-related diuretics.