The Release, Clearance and Plasma Protein Binding of Oxytocin in the Anaesthetized Rat

SUMMARY At 4°, the activity of exogenous 8-arginine vasopressin in rat plasma decreased to 50% in 2 days, whereas there was no loss of oxytocin under the same conditions after 3 days. At 37°, oxytocin was not inactivated in 9 hr., whereas 50% of 8-arginine vasopressin was lost in 2 hr. Forty per cent of exogenous oxytocin in rat plasma was unable to pass through a cellophane (Visking 8/32 in.) membrane, when subjected to a pressure of 100 torr for 18 hr. In rats under pentobarbitone anaesthesia, progressive haemorrhage of more than 2·0 ml./100 g. induced a secretion of both oxytocin and 8-arginine vasopressin, to produce maximum concentrations of 450 and 700 μ-u./ml., respectively, in the carotid plasma. In the intact rat (weighing 200–250 g.) anaesthetized with pentobarbitone, 50% of oxytocin in the circulation disappeared within 2 min. after stopping an i.v. infusion of 250–6000 μ-u./100 g./min. The half-time was increased to 4 min. by sham operation, and to 6 or 7 min. by occluding either the renal, or the portal, coeliac and mesenteric vessels. In non-lactating animals, the half-time was 8 min. after clamping both the renal and splanchnic vessels, whereas it was 6 min. in the lactating rat, under the same conditions. The apparent volume of distribution of oxytocin was 7·3 ml./100 g. in intact rats, and 10–13 ml./100 g. after operation. The plasma clearance of oxytocin was unaltered in the sham-operated rat, but it decreased after the operative procedures.