Diuretic and natriuretic effect of ebelactone B in anesthetized rats by inhibition of a urinary carboxypeptidase Y-like kininase

Ebelactone B (EB) (10(-7)-10(-5) M) inhibited dose-dependently Carboxypeptidase (CP) Y-like exopeptidase, one of the major kininases separated from rat urine, whereas it inhibited neither CPA, CPB or neutral endopeptidase (NEP). Degradation of bradykinin (BK) to BK-(1-8) in rat urine was completely inhibited by EB (10(-5) M) with the increased generation of BK-(1-7). Intraduodenal administration of EB (3 mg/kg) to anesthetized rats caused marked diuresis (by 110%) and natriuresis (130%), in parallel with the increase in urinary kinin levels (110%). Intravenous infusion of a BK antagonist, Hoe140 (3 mg/kg/hr), strongly blocked both EB-induced diuresis and natriuresis. EB may be a novel type of diuretic and natriuretic agent that acts by increasing urinary kinin levels.