OXYTOCIN-INDUCED NATRIURESIS MEDIATED BY THE RENAL KALLIKREIN-KININ SYSTEM IN ANESTHETIZED MALE-RATS

Intravenous infusion of oxytocin (OT) (10-100 nmol/kg/30 min) to 8-week-old anesthetized male rats resulted in a dose-dependent increase in urine volume, which showed a peak value 30-45 min after the start of OT-infusion. Urinary excretions of sodium, chloride and potassium were also increased by OT, showing peak values at 30-45 min, without any increase in the creatinine level. The natriuresis by OT was accompanied by increased excretion of urinary active kallikrein, which showed a peak value 15 min after the start of OT-infusion. The urinary kinin level was also increased. Intravenous infusion of a kallikrein inhibitor, aprotinin (15 mg/kg/90 min), when started 30 min before the OT-infusion, significantly inhibited the OT-induced increase in urine volume and urinary excretion of sodium, chloride and potassium. Intravenous infusion of a bradykinin B-2 antagonist, Hoe 140 (D-Arg[Hyp(3),Thi(5),D-TiC7,OiC(8)]BK, 4.5 mg/kg/90 min), when started 30 min before the OT-infusion, significantly inhibited the OT-induced increases in urine volume and urinary excretion of sodium and chloride, but not that of potassium. These results indicate that the OT-infusion induces natriuresis in male rats, and more than half of the natriuresis is mediated by a concomitant increase in excretion of urinary active kallikrein and the kinin generated.