Although it is generally accepted that organic mercurial diuretics depress the renal tubular absorption of sodium,2 precise localization of their site of action within the tubule has not been accomplished. If one administers graded doses of such diuretics to the dog it becomes apparent that, above a certain level, further increases in dosage yield progressively diminishing increments of sodium excretion. This pattern of response suggests that these agents depress some specific fraction of total sodium absorption, and that this fraction might be quantitated and the mechanism itself thereby identified by the administration of doses of mercurial diuretics sufficient to block it completely.The micropuncture studies of administered, they may well act on the distal tubule. This latter conclusion, in contrast to the first, is not incontestable. It is, of course, possible that there might be two or more distinct mechanisms for sodium absorption in the proximal tubule, only one of which is mercury sensitive. That mechanism might account for 16 to 33% of the total of 67 to 87%o of filtered sodium normally absorbed in the proximal tubule. Since no evidence of functional differentiation of sodium absorption in this segment exists, we incline to the former and simpler interpretation. Our findings demonstrate (a) that there is a specific mechanism for sodium absorption which can be completely blocked by large doses of mercurial diuretics; and (b) because it accounts for 17.1 to 21.4%o of total absorption, this mechanism probably resides in the distal tubule.
METHODSExperiments were performed on trained, unanesthetized dogs. Animals were used in the fasting state, at intervals of not less than one week. Glomerular filtration rate was measured by the creatinine clearance and sodium was determined in plasma and urine with an internal standard flame photometer. Other methods have been described in previous communications (3).
RESULTSThe unprepared, normally hydrated dog 3 is not suitable for this study. Presumably the loss of excessive quantities of sodium and water in the urine or the cardiac and vascular toxicity of the diuretic per se so compromises circulatory function that the animal cannot for long maintain a stable renal hemodynamic state. Consistently, the onset of diuresis is followed shortly by a fall in glomerular filtration rate such that the ap-
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