Acute tolerance development to the diuretic effect of furosemide in the rat

Furosemide was given to rats as five different i.v. bolus doses (2.5-100 mg kg-1), or as an i.v. infusion to a steady-state concentration in plasma of 14 micrograms ml-1. The urinary furosemide excretion rate (delta Ae/delta t) and the diuretic effect (volume of urine) were measured. A parallel shift in the excretion-response curve was seen as a fivefold increase in (delta Ae/delta t)50 [delta Ae/delta t) at half-maximal effect) between the i.v. bolus doses from 2.5 to 40 mg kg-1. The slope factor did not change. During infusion, a decrease in efficiency to 20 per cent of the initial value was seen. These results are indicative of an acute tolerance development to the diuretic effect of furosemide. Some intrarenal feedback inhibition mechanism might be involved, as the extracellular fluid volume seems to be of great importance to the effect obtained. The resulting effect can be compared with the influence of a competitive antagonist.