Diminution by captopril of the diuretic, natriuretic and kallikrein stimulating action of furosemide by reduction in its renal secretion.

The effect of furosemide (40 mg iv) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated without and with pretreatment by captopril (100 mg po). Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly (UNaV pre-C: +15, 1 +/- 2.1 ml/min vs. post-C: 7.0 +/- 0.3 ml/min; p less than 0.001). Similar changes in urinary kallikrein and kinin excretion were observed after captopril pretreatment, but because of the great coefficient of variation these changes did not reach statistical significance. The reason for the reduced activity of furosemide after captopril pretreatment was the diminished proximal-tubular secretion of furosemide, as it could be shown by direct measurement of the drug in urine. After furosemide injection changes in plasma aldosterone concentration paralleled changes in renal kallikrein and kinin excretion. However, after captopril there was a sharp dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion.