The present series of work were undertaken in order to clarify some of the clinical problems, such as modes of administration, refractriness and side effects. Among the various diuretics, acetazoleamide, mercurials and chlorothiazide were chosen, since these are used most widely and have most interesting problems about their actions. I studied the mechanism of the action, the electrolyte dirturbances caused by them and the factors influencing the action. Studies on the mechanism of the action were made mainly by the stop-flow method, which were proved as a reliable and excellent method to study the localisation of the reabsorption and secretion in the nepheon. The action of mercurials on the potassium excretion was examined by other methods, because the stop-flow method is not proper to examine the potasium transport. As a factor influencing the action of diuretics, I layed emphasis on the intracellular potassium and hydrogen ion metabolism, which is the most direct circumstance where diuretics preform their actions.(1) Acetazoleamide depresses the reabsorption of bicarbonate in both proximal and distal tubules, but depresses the reabsorption of sodium only in the proximal tubule. Mercurials depress the reabsorption of sodium in the proximal tubule. The secretion of potassium is depressed by mercurials, and the reabsorption of potassium is also considered to be depressed by the mercurials. such an action on the potassium excretion is specific to mercurials, but are influenced by the adrenal cortical hormones. Chlorothiazide enhances the excretion of sodium, potassium, chloride and bicacbonate. The mechanism to increase the potassium excretion, however, is different from that of acetazoleamide, and the mechnism to increase the chloride excretian is different from that of mercurials. The data suggest that chlorothiszide depresses the reabsorption of sodium and chloride not only in the proximal tubule, but in the distal tubule. (2) Acetazoleamide may cause hypokalemic acidosis, mercurials hypochl.oremic alkalosis, and Chlorothiazide hypokalemic alkalosis. (3) Acidifing salts depress the action of acetazoleamide, and increase the action of mercurials. Alkalinizing salts depress the action of mercurials and increase the action of acetazolea-mide. Chlorothiazide are scarecely influenced by either salts. (4) The intracellular potassium concentration are influe need by the change of acid-base balance, and reveresely the ineracellular acid-base balance is influenced by the change of potassium metabolism. These intracelluar electrolyte metabolism must be considered as an important factor which influences the acitons of acetamoleamide and mercurials. (5) DOCA and Pitressin have no influence on the mercurial diuresis. DOCA, horever, can influence the mode of electrolyte excretion during the mercurial diuresis.
