Role of endogenous prostaglandins in volume expansion and during furosemide infusion in conscious dogs

The renal effects of two structurally dissimilar inhibitors of prostaglandin synthesis (Meclofenamate and RO-20-5720) were studied in conscious, chronically instrumented dogs during mild volume expansion and during a constant infusion of furosemide. When either inhibitor was administered following volume expansion, urinary excretion of PGE₂and urine flow rate were reduced by more than 50%. In contrast, renal plasma flow fell by less than 10% while glomerular filtration rate, sodium excretion, and plasma renin activity (PRA) were unchanged. In separate studies, infusion of furosemide increased renal plasma flow, urine flow rate, sodium excretion, PRA, and urinary excretion of PGE₁while glomerular filtration rate decreased. Administration of inhibitors of prostaglandin synthesis during constant infusion of furosemide reduced the urinary excretion of PGE₂to control levels, as renal plasma flow and glomerular filtration rate fell below control level. Despite these hemodynamlc alterations, the furosemide-induced diuresis and increase in PRA were only partly attenuated by prostaglandin inhibition. It is concluded that in conscious dogs, intrarenal prostaglandins modulate urine flow rate during mild volume expansion and play a major role in mediating the renal hemodynamic effects of furosemide.