FUROSEMIDE RENAL EXCRETION RATE AND THE EFFECTS OF THE DIURETIC ON DIFFERENT TUBULAR SITES ARE MODIFIED BY ENDOGENOUS DOPAMINE IN NORMOHYDRATED RATS

The present study was designed to explore the involvement of endogenou s dopamine in furosemide excretion and in the actions of the diuretic on tubular sodium reabsorption. The dose-response relationship for the diuretic effect of furosemide given as i.v. bolus injections (0.2-7.5 mg . kg(-1)) was studied by clearance technique in pentobarbital-anes thetized rats treated with vehicle, benserazide (BZ) (25 mg . kg(-1) i .v.) or SCH 23390 (50 mu g . kg(-1) + 10 mu g . kg(-1) . min(-1) i.v.) . Furosemide induced the maximal diuresis 15 to 30 min after i.v. admi nistration. The diuretic response was dose-dependent and was reduced i n the animals treated with BZ and SCH 23390. Fractional sodium excreti on was also increased by furosemide from 1.8 to 7.5% during the same p eriod. This effect was reduced by both BZ or SCH 23390 by 35 to 50%. T he effects of furosemide on proximal and distal renal tubules were dis sected by measuring the renal lithium clearance (CLi+). Furosemide eff ects on proximal tubular sites (measured by FE(Na) + prox = CLi+/Cln) were completely abolished by BZ and SCH 23390, whereas both drugs redu ced furosemide effects on distal tubular sites (measured by FE(Na) + d istal= CNa+/CLi+) by 20 to 40%. Furosemide excretion rate during the p eak response to the diuretic was measured in the urine. BZ and SCH 233 90 diminished furosemide excretion by 45 to 80% as compared with vehic le-treated animals. The furosemide tubular effects and the proximal an d distal functions measured by CLi+ determined during the peak respons e were correlated to the maximal excretion rate of furosemide in the u rine. Excretion-response curves were similar for urine flow, fractiona l sodium excretion and distal fractional sodium reabsorption in the ve hicle-, BZ- or SCH 23390-treated animals, but they were different for proximal fractional sodium reabsorption. Our findings suggest that the stimulation of D-1 receptors by endogenous dopamine can facilitate th e excretion of furosemide and that D-1 tubular receptors are also invo lved in the inhibition of proximal fractional sodium reabsorption elic ited by the diuretic.