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 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)
Nowicki
S
S
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Opezzo
J A
JA
Levin
G
G
Gonzalez
D
D
Elias
M M
MM
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
D001552:Benzazepines; D004232:Diuretics; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D001545:Benserazide; D005665:Furosemide; D004298:Dopamine