Effect of vanadate on fluid absorption and PAH secretion in isolated proximal tubules

Abstract

Although vanadate, a potent inhibitor of Na+-K+-ATPase, causes marked natriuresis in vivo and inhibits p-aminohippurate (PAH) accumulation in renal cortical slices, the nephron sites of action were not previously investigated by in vitro methods. The effects of bath and luminal vanadate were examined on net fluid absorption (Jv) and PAH secretion .**GRAPHIC**. in S1 and S2 segments of the rabbit proximal tubule. One .mu.mol vanadate in the perfusate produced maximal inhibition of Jv in S1 (from 1.00 .+-. 0.05 to 0.72 .+-. 0.06 nl/min per mm) but had no effect on Jv in the S2 segment. Vanadate (100 .mu.M) added only to the bath had no effect on Jv in either segment. In S1 and S2, luminal vanadate inhibited .**GRAPHIC**. to a similar extent and in a dose-dependent manner. At 10 .mu.M luminal vanadate .**GRAPHIC**. was inhibited by 27% in S1 and 35% in S2. Increasing extracellular K+ from 5-10 mM in both the bath and perfusate potentiated the inhibitory effect of luminal vanadate on Jv and .**GRAPHIC**. Vanadate did not increase tubule permeability, as the efflux of PAH and inulin from lumen to bath was not changed and ouabain reduced Jv to 0 in the presence of vanadate. Apparently, vanadate inhibits both Jv and .**GRAPHIC**. in rabbit proximal tubules and is more effective from the luminal than from the bath side. The potentiation of the inhibitory effect on Jv by K supports the view that vanadate alters Na absorption in proximal tubules by inhibiting Na+-K+-ATPase.