Effects of frusemide on the renal kallikrein-kinin system of the rat.

1. In male Wistar rats, three doses of frusemide (0.5, 5.0 and 50.0 mglkg) were injected subcutaneously. A dose-related increase in urine flow and natriuresis occurred, whereas there was a biphasic response in kallikrein excretion with an initial, dose-related transient increase and a secondary reduction. When the urine losses were replaced by the infusion of 0-99/0 NaCl solution, the biphasic response of urinary kallikrein excretion was maintained. 2. In all experiments, urinary excretion of kallikrein correlated with the excretion of potassium. Frusemide enhanced the excretion of kinins, which correlated with the urine volume and the natriuresis, but not with kallikrein excretion. 3. In contrast to the initially increased excretion of kallikrein, kallikrein activity in the renal cortex remained unchanged or was even reduced. Kininogen content of the perfused tissue of the renal cortex did not vary throughout the experiment, but decreased markedly in the non-perfused tissue of the cortex 30 min after the injection of frusemide. 4. It is concluded that forced diuresis induced by frusemide causes a ‘wash out’ of renal kallikrein in urine, probably not indicating the true changes in the activity of the renal kallikrein-kinin system within the kidney. Kinin excretion in urine was not correlated with kallikrein excretion but with changes in diuresis. Thus it might be suggested that the renal kallikrein-kinin system could be involved by