Prostaglandins May Modulate the Aldosterone Response to ACTH in Sodium Restricted Normotensives

Aldosterone production following ACTH administration has been shown to be enhanced in sodium depletion. The mechanism (s) for this, however, is not entirely clear. Meanwhile, prostaglandins of the E series have been shown to stimulate steroidogenesis and urinary excretion of prostaglandin E2 and F2α in man, and PGI2 in the aortic wall of rats has been shown to increase in sodium depletion.In view of the above findings the present study was undertaken to evaluate the involvement of the endogenous prostaglandins in the augmentation of ACTH-induced aldosterone response during acute sodium depletion. Captopril was administered to elucidate the influence of the renin-angiotensin system (250mg q.i.d.) and Indomethacin (Ind) to suppress the production of the endogenous prostaglandins (200mg q.i.d.). Group I were on a diet containing 200mEq/day sodium and sodium depletion was achieved by a low sodium diet containing 60mEq/day sodium and oral treatment of fulosemide 80mg for 1 day (groups II, III and IV). Ind was given in group II, Ind + captopril in group III and captopril in group IV. The i.m. administration of 250μg ACTH was performed at 0800-0900h.Body weight, serum sodium and potassium levels on the day of the experiment were significantly lower in groups II, III and IV versus group I. Basal PRA. in groups III and IV were more significantly elevated than groups I and II. Basal plasma 6-keto-PGF1α levels were significantly lower than in the Ind pretreated groups (II, III). There were no significant differences between baseline plasma aldosterone and cortisol concentrations.In groups I, II and III, plasma aldosterone increased from baseline levels to 182%, 134%, 193% respectively, following the ACTH administration, and there were no significant differences in mean increment among the three groups. In group IV, however, plasma aldosterone increased from 6.4 ± 0.9 ng/dl to 32.1 ± 4.9ng/dl and 26.1 ± 3.9 ng/dl at 30 and 60 min. after the ACTH administration respectively, a mean increment of 468%. This response was significantly greater than those of the three other groups. Plasma cortisol response to ACTH administration was similar in all four groups. The augmented response to ACTH was not affected by angiotensin I converting enzyme inhibitor, captopril however, significantly reduced the response in Ind pretreated groups.It is suggested that endogenous prostaglandins may modulate augmented ACTH induced aldosterone response in a sodium depleted state in man.