Involvement of renal dopamine synthesis in the diuretic effect of furosemide in normohydrated rats.
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.
Nowicki
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S
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Levin
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G
Enero
M A
MA
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
D017447:Receptors, Dopamine D1; D007980:Levodopa; D001545:Benserazide; D005665:Furosemide; D012964:Sodium; D004298:Dopamine