title: Furosemide renal excretion rate and the effects of the diuretic on different tubular sites are modified by endogenous dopamine in normohydrated rats.
abstract: 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.kg-1) was studied by clearance technique in pentobarbital-anesthetized rats treated with vehicle, benserazide (BZ) (25 mg.kg-1 i.v.) or SCH 23390 (50 micrograms.kg-1 + 10 micrograms.kg-1.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 effective on proximal tubular sites (measured by FENa+ prox = CLi+/Cln) were completely abolished by BZ and SCH 23390, whereas both drugs reduced furosemide effects on distal tubular sites (measured by FENa+ 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Nowicki
authors.forename: J A
authors.initials: JA
authors.lastname: Opezzo
authors.forename: G
authors.initials: G
authors.lastname: Levin
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez
authors.forename: M M
authors.initials: MM
authors.lastname: Elias
mesh_terms: D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology* / Q000652:urine; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000493:pharmacokinetics*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D009318:Natriuresis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001552:Benzazepines; D004232:Diuretics; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D001545:Benserazide; D005665:Furosemide; D004298:Dopamine