Since the appearance in 1887 of von Schroeder's first publication (1) concerning the action of xanthine diuretics there has been much debate regarding the mechanism by which these substances produce diuresis. Similarly there has been considerable controversy as to the manner in which salyrgan and other organic mercury compounds increase the output of urine. REVIEW OF LITERATUREIn the earlier work on xanthine diuresis investigators were chiefly interested in distinguishing between direct action on the renal cells and effects produced through changes in renal circulation. Von Schroeder (1) (2) concluded from his experiments that the effect of caffeine and related substances upon urine output was independent of circulatory changes. Loewi, Fletcher and Henderson (3) held the opposite point of view. They confirmed the observation, first made by Phillips and Bradford (4), that caffeine usually increases the volume of the kidney and considered this as evidence that diuresis was caused by dilatation of the renal blood vessels. Although this observation concerning kidney volume during caffeine diuresis is generally accepted, its significance has been questioned by Gottlieb and Magnus (5) because diuresis sometimes occurs without increase in kidney volume, by Brings and Molitor (6) who concluded that the increase in volume was of too short duration to be significant, and by Cushny (7) who pointed out that increase in kidney volume does not necessarily indicate vasodilatation.

There are conflicting reports in the literature concerning the effect of the mercurial diuretics upon the water content of the plasma. Saxl and Heilig (1), Bohn (2, 3) and Crawford and McIntosh (4) have reported that the concentration of protein in the plasma falls before the onset of novasurol diuresis. Miihling (5), Nonnenbruch (6) and Bleyer (7), on the other hand, found no such evidence of plasma dilution.In a previous publication (8) evidence was presented that salyrgan diuresis is the result of decreased reabsorption of water in the renal tubules. It was suggested that this decrease in reabsorption is produced by a depressant action of the drug on the tubular epithelium. The occurrence of hydremia preceding the onset of diuresis would be inconsistent with this hypothesis and would point to a primary extrarenal action, occurring alone or in conjunction with a direct action on the kidney. Carefully controlled studies of the effect of salyrgan upon the refractive index of the plasma have, therefore, been carried out. For purposes of comparison similar studies have been made with intravenously administered physiological saline solution. PROCEDUREThe experiments were performed upon unanesthetized female dogs who lhad gone without food for twelve hours or more. In Control Experiments 1 to 7 inclusive, and in the first seven salyrgan experiments, the animals were permitted to drink water as desired until two hours before the beginning of the experiment. In all other experiments the dogs were allowed no water for five hours preceding the period of observation. During the experiment the dog was tied down on a table. After a period of training the animals would remain in this position for two to three hours without struggling. Urine was collected from the bladder directly into graduated cylinders by an inlying catheter. Blood samples were drawn from the external jugular vein without stasis. Heparin (0.01 cc. of a 4 per cent solution to each cc. of blood) was used to prevent clotting. In Control Experiments 1, 2, 3, and 4 and in salyrgan Experiments 1 and 2 the blood 741

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