Effect of Meralluride on Solute and Water Excretion in Hydrated Man: Comments on Site of Action*

The renal tubular site at which organomercurials exert their primary effect on salt absorption has been the subject of considerable dispute for many years. The fact that these drugs produced a consistent reduction in Tmglucose and TmPAH in man suggested that these agents exerted an influence within the proximal tubule (1, 2). The absence of such changes in the dog, despite comparable diuretic activity, emphasized the hazards of such conclusions (3). Other experimental studies in- dicating that distal tubular functions such as the production of ammonia and titratable acid were not influenced by the administration of mercurials, were also used to imply a primary proximal tu- bular effect (4). Potassium secretion, however, which represents a late distal operation was shown to be depressed by the mercurial agents (5, 6). In hydrated man, it was demonstrated that meralluride produced a prompt increase in the rate of excretion of "nonsolute obligated" wa- ter implying a proximal tubular effect on salt and water absorption (7, 8). On the other hand, other observers reported that the administration of organomercurials to hydrated man and dog did not change the rate of free water clearance (9, 10). Recently, utilizing the stop flow technique, several investigators have concluded that, in the dog, the major site of action of the organic mer- curials is confined to the proximal tubule