Acute Tolerance to Furosemide. Pretreatment with Captopril or Prazosin does not Influence Diuresis and Natriuresis

Abstract

To investigate whether the development of acute tolerance to furosemide in human subjects could be prevented or delayed by angiotensin converting enzyme inhibition or α₁-receptor blockade, a study was conducted on healthy volunteers. The protocol on the experimental days was identical except for pre-treatment with placebo, captopril or prazosin. During continuous furosemide infusion with urinary furosemide excretion at a constant rate, the subjects became progressively dehydrated, with a maximal decrease in plasma volume of 9–11%. The diuretic/natriuretic response to furosemide was similar in the three protocols. Acute tolerance to diuresis developed earlier than that to natriuresis, again with no differences between the protocols. Not until the plasma volume had decreased by 9% did the natriuresis diminish significantly. In the placebo and captopril protocols acute tolerance was caused mainly by a decreased glomerular filtration rate, and in the prazosin protocol mainly by increased tubular reabsorption. It is concluded that neither ACE inhibition nor α₁-receptor blockade prevented or delayed the acute tolerance to furosemide. The results suggest that acute tolerance to furosemide can be induced through different but complementary homeostatic mechanisms in the kidney.