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 B2 antagonist, Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]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.
Adachi
K
K
Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
Katori
M
M
Nishijima
M
M
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002712:Chlorides / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000652:urine; D007705:Kinins / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
D002712:Chlorides; D007705:Kinins; D010121:Oxytocin; C065679:icatibant; D012964:Sodium; D003404:Creatinine; D007610:Kallikreins; D011188:Potassium; D001920:Bradykinin