title: Involvement of renal dopamine synthesis in the diuretic effect of furosemide in normohydrated rats.
abstract: The present study was designed to investigate whether the modification of dopamine synthesis affects furosemide responses. Experiments were performed on pentobarbital-anesthetized rats. Basal urine flow was approximately 3 microliters/min-1/g-1 of kidney weight (k.w.); furosemide (0.2 mg/kg-1 i.v.) induced a rapid diuretic effect (19.3 +/- 1.4 microliters/min-1/g-1 of k.w.). The dopadecarboxilase inhibitor, benserazide (25 mg/kg-1 i.v.), reduced furosemide-induced diuresis to 8.3 +/- 2.1 microliters/min-1/g-1 of k.w., whereas levo-dihydroxyphenylalanine (L-dopa; 1 micrograms/kg-1/min-1 infused for 60 min) increased it to 41.4 +/- 6.1 microliters/min-1/g-1 of k.w. Natriuretic response and fractional Na+ excretion induced by furosemide were significantly lower in benserazide-treated and higher in L-dopa-treated animals. Urine dopamine (DA) excretion was enhanced by furosemide from 0.44 +/- 0.05 to 0.98 +/- 0.22 ng/min-1/g-1 of k.w. and was markedly reduced in benserazide-pretreated animals, whereas both basal DA excretion and that induced by furosemide were increased significantly during L-dopa infusion. However, in benserazide- or L-dopa-treated animals, basal urine flow was not different from the control group. Urine furosemide excretion was reduced by 60% by benserazide treatment and increased by 62% during L-dopa infusion. The results are consistent with the suggestion that although endogenous DA is apparently unimportant in the maintenance of basal urine output, it is involved in furosemide-induced diuresis. The diuretic response can be altered by acute administration of substances that affect dopamine synthesis.
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: G
authors.initials: G
authors.lastname: Levin
authors.forename: M A
authors.initials: MA
authors.lastname: Enero
mesh_terms: D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004298:Dopamine / Q000096:biosynthesis* / Q000652:urine; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D012964:Sodium / Q000378:metabolism
chemical_list: D017447:Receptors, Dopamine D1; D007980:Levodopa; D001545:Benserazide; D005665:Furosemide; D012964:Sodium; D004298:Dopamine