Furosemide renal excretion rate and the effects of the diuretic on different tubular sites are modified by endogenous dopamine in normohydrated rats

Nowicki, S.; Opezzo, J.A.; Levin, G.; Gonzalez, D.; Elias, M.M.

Journal of Pharmacology and Experimental Therapeutics 274(3): 1348-1354

1995


ISSN/ISBN: 0022-3565
PMID: 7562507
Document Number: 447783
The present study was designed to explore the involvement of endogenous 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 cntdot kg-1) was studied by clearance technique in pentobarbital-anesthetized rats treated with vehicle, benserazide (BZ) (25 mg cntdot kg-1 i.v.) or SCH 23390 (50 mu-g cntdot kg-1 + 10 mu-g cntdot kg-1 cntdot min-1 i.v.). Furosemide induced the maximal diuresis 15 to 30 min after i.v. administration. The diuretic response was dose-dependent and was reduced in the animals treated with BZ and SCH 23390. Fractional sodium excretion was also increased by furosemide from 1.8 to 7.5% during the same period. This effect was reduced by both BZ or SCH 23390 by 35 to 50%. The effects of furosemide on proximal and distal renal tubules were dissected by measuring the renal lithium clearance (CLi+). Furosemide effects on proximal tubular sites (measured by FE-Na + prox = CLi+/Cln) were completely abolished by BZ and SCH 23390, whereas both drugs reduced furosemide effects on distal tubular sites (measured by FE-Na + distal= CNa+/CLi+) by 20 to 40%. Furosemide excretion rate during the peak response to the diuretic was measured in the urine. BZ and SCH 23390 diminished furosemide excretion by 45 to 80% as compared with vehicle-treated animals. The furosemide tubular effects and the proximal and distal functions measured by CLi+ determined during the peak response were correlated to the maximal excretion rate of furosemide in the urine. Excretion-response curves were similar for urine flow, fractional sodium excretion and distal fractional sodium reabsorption in the vehicle-, 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 the excretion of furosemide and that D-1 tubular receptors are also involved in the inhibition of proximal fractional sodium reabsorption elicited by the diuretic.

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