Bumetanide-induced natriuresis and antinatriuresis in the proximal and distal parts of the human nephron. Investigations in acute and chronic bumetanide treatment.
In the present study we used the Li clearance technique to evaluate the effects of submaximal bumetanide infusion on proximal and distal Na reabsorption in healthy volunteers with and without volume and Na replacement. These effects were studied both in chronic bumetanide-treated and in previous nontreated subjects. Li was given as Li carbonate p.o. Glomerular filtration was evaluated by creatinine clearance. Infusion of bumetanide increased fractional Na excretion and fractional Li excretion in the volume-replaced subject. Without volume-replacement bumetanide infusion increased these excretion rates to a significantly lower level. These results suggest that in humans acute submaximal doses of bumetanide cause inhibition of both proximal and distal tubular reabsorption of Na. Along with diuretic-induced volume contraction the natriuretic response is diminished perhaps due to a secondary increase in fractional Na reabsorption which occurs only in the proximal tubular portions of the nephron. In chronic bumetanide-pretreated subjects, however, the fractional Na and Li excretion increased significantly more than in the previous nontreated subjects. Compared to these ion excretions in diuretic-induced Na and volume-depleted subjects the results suggest that a secondary increase in fractional Na reabsorption is developed rapidly during submaximal bumetanide infusion in chronic bumetanide-treated subjects. In the distal part of the nephron, however, the bumetanide-induced increase in Na excretion is much less in the chronic bumetanide-treated subjects than in previous nontreated. Because of these results it is suggested that simple dose-effect relationship for loop-diuretics will be difficult to describe.
Staalsen
N H
NH
Division of Clinical Pharmacology, University of Aarhus, Denmark.
Steiness
E
E
D000328:Adult; D002034:Bumetanide / Q000008:administration & dosage / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
D004232:Diuretics; D002034:Bumetanide; D008094:Lithium; D012964:Sodium