Interrelationships between the renal kallikrein-kinin and prostaglandin systems in furosemide-induced diuresis.

Abstract

The relationships between the renal kallikrein-kinin (K-K) and prostaglandin (PG) systems under conditions of furosemide-induced diuresis were studied in normal rats. Urinary PGE and PGF2 alpha were measured by radioimmunoassay, and urinary kallikrein by enzymatic activity. The diuretic and natriuretic effects of furosemide were accompanied by a concomitant increase in the urinary excretion of kallikrein and PGE. The urinary excretion of kallikrein and PGE was closely related to the urinary excretion of sodium, potassium and chloride. The urinary excretion of kallikrein also showed a highly significant correlation with the urinary excretion of PGE. Pretreatment of the animal with indomethacin or aprotinin inhibited furosemide-induced diuresis and natriuresis. Aprotinin inhibited the urinary excretion of PGE, while indomethacin did not exert any inhibitory action on the urinary excretion of kallikrein. Although the urinary excretion of kallikrein was closely related to the urinary excretion of potassium, both indomethacin and aprotinin had no effect on the urinary excretion of potassium. The results indicate that the potassium-sodium exchange caused by furosemide in the distal nephron might stimulate the renal K-K system to result in increasing synthesis of PGE, which would, at least in part, participate in the diuretic and natriuretic effects of furosemide.