On the mechanism of acute tolerance to furosemide diuresis.
The renal response to continuous furosemide infusion (8 mg/h) and subsequent ECV changes was studied in 8 healthy volunteers. Furosemide increased urine flow from a basal flow of 4.3 ml/min to a maximum of 15.4 ml/min. During dehydration (-1.8 kg) the diuresis decreased to 8.4 ml/min. The sodium, chloride and potassium excretion likewise decreased. This reduction in diuretic effect (acute tolerance) was accompanied by significantly increased plasma levels of norepinephrine (1.38 to 2.14 nmol/l), PRA (0.52 to 1.13 ng/ml/h) and aldosterone (0.29 to 0.45 nmol/l). After rehydration the urine flow increased to 23.1 ml/min. The changes in diuretic response from initial effect to the dehydrated state and after rehydration were mainly a consequence of changed renal sensitivity to furosemide (urinary excretion of 21 to 14 to 35 mumol Na+ per microgram furosemide excreted). It is proposed that activation of the sympathetic nervous system and/or the renin-angiotensin-aldosterone system may play a role in mediating the acute tolerance to furosemide diuresis. The relative importance of each remains to be clarified.
Sjöström
P A
PA
Department of Internal Medicine, Orebro Medical Center Hospital, Sweden.
Odlind
B G
BG
Beermann
B A
BA
Hammarlund-Udenaes
M
M
D000328:Adult; D000450:Aldosterone / Q000097:blood; D004231:Diuresis / Q000187:drug effects*; D004298:Dopamine / Q000097:blood; D004361:Drug Tolerance; D005665:Furosemide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007444:Inulin; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000450:Aldosterone; D005665:Furosemide; D007444:Inulin; D012083:Renin; D004298:Dopamine; D009638:Norepinephrine