Furosemide compounds enhance urinary excretion of active kallikrein independently of their effects on urinary electrolyte excretion

The chemical and diuretic effects of furosemide on the excretion and activation of urinary prokallikrein were investigated in rats by treatment with furosemide compounds with a range of diuretic activity or amiloride hydrochloride or the vehicle. Diuresis occurred with furosemide and benzyl furosemide, but not with isofurosemide, amiloride hydrochloride, or the vehicle. The urinary excretion rate of active kallikrein was significantly elevated above controls throughout the 72 h of treatment with all of the drugs tested, regardless of the level of diuresis or the rate of urinary electrolyte excretion. In contrast, the urinary excretion rate of total kallikrein (prokallikrein + active kallikrein) was unchanged in all groups. These data indicate that furosemide derivatives increase the activation, but not the excretion, of urinary prokallikrein and that these effects are unrelated to the chemical structure or diuretic activity of the compounds or to overall changes in urinary electrolyte excretion rates.