Interaction between furosemide-induced renal vasodilation and the prostaglandin system

Abstract

The effect of intravenous furosemide, 5 mg/kg, on renal hemodynamics as it relates to the prostaglandin cascade was examined in dogs. In 11 dogs the vasculature to the kidney was isolated and a femoral to renal arterial and a renal to femoral venous shunt was performed. With the use of a protein-free salt solution to perfuse the kidney for 3 minutes, the renal cortex was enriched with tritiated arachidonic acid. After blood perfusion to the kidney was re-established, the renal effluent radioactivity was followed before and after furosemide administration. Furosemide produced two types of response. In six dogs there was renal vasodilation, diuresis, and a three and one-half fold increase in renal venous radioactivity. In five dogs that were in renal failure, furosemide administration caused no change in renal blood flow, no diuresis and no increase in renal venous effluent radioactivity. On thin-layer chromatography most of the released radioactivity by the kidney after furosemide administration traveled as arachidonic acid. In a separate seven dogs, we measured the total unesterified arachidonic acid concentration in the plasma before and after furosemide by the use of gas chromatographyflame ionization. Even though in these dogs furosemide caused a significant increase in renal blood flow and diuresis, renal venous plasma levels of arachidonic acid were unaltered. Our data suggest that furosemide causes a release of arachidonic acid from the kidney from a small pool of fast turnover lipid stores and that the stimulus for arachidonic acid release after furosemide depends on an intrarenal mechanism whereby the diuresis is coupled to the increase in renal blood flow.