Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats.
The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of 14C-tetraethylammonium, 3H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (CLi/CIn) and the distal nephron segments (CNa/CLi). The changes in CLi/CIn became maximal at doses above 0.5 mg/kg, whereas CNa/CLi was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of CNa/CLi. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment.
Shalmi
M
M
Department of Pharmacology, University of Copenhagen, Denmark.
Petersen
J S
JS
Christensen
S
S
D000818:Animals; D002034:Bumetanide / Q000008:administration & dosage / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007684:Kidney Tubules; D007686:Kidney Tubules, Distal / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008094:Lithium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*
D004232:Diuretics; D002034:Bumetanide; D008094:Lithium; D012964:Sodium