S. Nowicki et al., FUROSEMIDE RENAL EXCRETION RATE AND THE EFFECTS OF THE DIURETIC ON DIFFERENT TUBULAR SITES ARE MODIFIED BY ENDOGENOUS DOPAMINE IN NORMOHYDRATED RATS, The Journal of pharmacology and experimental therapeutics, 274(3), 1995, pp. 1348-1354
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.