Abstract

Substitution of the amino acid glycine for 7-proline in oxytocin produces an analog, [7-glycine]oxygocin, having markedly reduced antidiuretic and vasopressor activities but retaining considerable natriuretic activity. We administered this analog alone and with distally acting diuretic agents to test the hypothesis that oxytocin and its analogs decrease proximal tubular fluid reabsorption. If [7-glycine]oxytocin shares a common mechanism of action with any of these agents, the response to combined treatment should be less than additive, otherwise, the saluretic effect of both agents should be maintained. Subcutaneous administration of [7-glycine]oxytocin, 10 micrograms/kg, to conscious fluid-loaded rats produced a natriuresis, diuresis and kaliuresis. Hydrochlorothiazide and [7-glycine]oxytocin administered together to the same rats had a greater than additive effect on urine volume and sodium excretion. Furosemide and [7-glycine]oxytocin had an additive effect on urine volume, sodium and chloride excretion. Triamterene blocked the kaliuresis caused by [7-glycine]oxytocin, although the two agents administered together had a greater than additive effect on sodium excretion. These results indicate that [7-glycine]oxytocin does not share a common natriuretic mechanism or site of action with the above diuretics. Our data are consistent with the hypothesis that oxytocin and its analogs may increase urinary sodium excretion by decreasing net proximal tubular fluid reabsorption.