Metabolic Effects of Progesterone in the Dog

Abstract

Progesterone has been reported to be natriuretic ( 1 4 ) and catabolic (4-6) in man. Kagawa et al. (7) demonstrated natriuresis in the rat. Progesterone was also shown to elevate peripheral plasma renin activity (PPRA) in the dog (8). Both in vivo (3,4) and in vitro (9) studies suggest that the natriuretic effect is through the blocking of aldosterone action. The purpose of the present investigation was to study the metabolic effects of progesterone in the dog and attempt to correlate them with changes in PPRA.Materials and Methods. Four female mongrel dogs, weighing 16-25 kg, were maintained in metabolic cages; and complete 24-hr urine collections were obtained by daily bladder catheterizations. The dogs were initially placed on a sodium diet containing approximately 3 5-40 meq (normal sodium diet) for 30 days. On this diet PPRA was assayed on alternate days and daily urinary sodium and urea excretion were measured. After initial stabilization, a synthetic proges-terone4 (200 mg, im/day) was administered for 6 days. The dogs were then allowed to stabilize for another 6 days and an aldosterone antagonist (spironolactone, 300 mg/ day, po) was administered in the diet for 5 days. The dogs were then placed on a sodium diet containing 3-6 meq/day (low sodium diet) and were allowed to stabilize for one week. The same studies utilizing prowith certification of chemical analysis. 40 VI CT I N 30 z CONTROL RECOVERY L --63 S P I R O N O L A C T O N E 0 , -; ; 20 v -x W 5 3 10 n 0 VI 0 N O R M A L LOW S O D I U M D I E T S O D I U M D I E T FIG. 1. Effects of progesterone and spironolactone on sodium excretion.gesterone and spironolactone were then repeated on this diet.The bloods for PPRA were drawn into heparinized tubes and immediately centrifuged in the cold, and the plasma was separated and frozen. The PPRA was measured by a modification of the method of Helmer ( 10) as described by Boonshaft et al. (1 1).Renin activities are expressed in terms of nanograms of angiotensin I1 generated per milliliter of plasma per hour of incubation. Urinary sodium was determined with an IL flame photometer using an internal lithium standard. Urinary urea was measured by the urease method ( 12 ) .Results. On the normal sodium diet, the control sodium excretion was 37.4 t 1.3 meq/24 hr (mean t SEM) and the control urea excretion was 5.71 t 0.38 gJ24 hr. After progesterone administration, the sodium excretion was 32.2 -+ 1.9 meq/24 hr ( p > .05) and the urea excretion was 5.65 t_ 0.29 g/24 hr (Table I) which also was not significant ( p > .05). After spironolactone administration, the urinary sodium excretion was 37.2 t 2.3 meq/24 hr (Fig.