Dose dependence of proximal and distal tubular effects of furosemide in conscious rats.

The dose-response relationship for the diuretic effect of furosemide, given as i.v. bolus injections (0.1-480 mg/kg) was investigated by clearance technique in conscious rats. By measuring the renal Li clearance, the effects on proximal and distal nephron segments were separated, and peak responses were correlated to the maximal excretion rate of furosemide in the urine. At the highest dose of furosemide, fractional Na excretion was increased from 1 to 19%, due to inhibition of fractional proximal Na reabsorption from 65 to 40% and fractional distal Na reabsorption from 97 to 57%. Furosemide inhibition of fractional proximal Na reabsorption showed a maximum at intermediate doses (7.5 mg/kg), whereas there was no maximum for the inhibition of distal fractional Na reabsorption. The natriuretic response was shorter than expected from the decline in furosemide excretion due to an abrupt fall in glomerular filtration rate and a rapid normalization of proximal fractional Na reabsorption. It is suggested that the maintenance of a normal delivery of tubular fluid to the distal nephron during furosemide-induced volume contraction may be due to inhibition of proximal tubular reabsorption.