A substance was isolated from the urines of normotensive and hypertensive subjects undergoing salt load experiments. This substance was tested in rats for its natriuretic properties. It was found that both groups excrete a natriuretic material. The natriuretic activity of the material isolated from hypertensive subjects, who responded to the salt loading procedure with an exaggerated natriuresis, was significantly higher than that deriving from normotensive subjects.

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The diuretic and saluretic response to the intravenous infusion of a 5% salt solution (5 g of NaCl/m² of body surface area) was examined in a group of normotensive subjects, in patients with uncomplicated essential hypertension, in normotensive women after toxemia of pregnancy and in subjects with ‘labile’ hypertension, who were normotensive at the time of the study. It was found that the 2 latter groups reacted to the procedure in a very similar manner as the subjects with hypertension, i. e. with a diuretic as well as saluretic response of rapid onset, in contrast to the gradual and much lesser rise in water and salt excretion observed in the normal control subjects. The diuretic response in all 3 experimental groups was more pronounced than the saluretic response. The use of a salt loading test appears to be useful in epidemiological and prospective studies on hypertension.

Previous studies (1) from this laboratory have indicated that urinary excretion of mercury reaches a maximal value immediately following the intravenous injection of an organic mercurial diuretic and then falls rapidly, presumably as the plasma concentration of mercury decreases. Moreover, the dynamics of mercury excretion during the first four to six hours in a given individual are quite constant on repeated measurement and are not significantly affected by certain factors which either enhance or inhibit diuresis.In the present study the mechanisms by which mercury is removed from the plasma and excreted in the urine and the relationship of this process to mercurial diuresis have been investigated in human subjects with the aid of simultaneous measurements of renal hemodynamics, urinary mercury and electrolyte excretion, and arterial and renal venous plasma mercury concentrations. MATERIALS AND METHODSOf the six patients in this group, four were presumably free from renal disease. One patient (S. F.) had only one (right) kidney; another (W. M.) was recovering from glomerulonephritis.All studies were carried out in the post-absorptive state. A multi-holed, soft rubber catheter was inserted in the urinary bladder. After placing an indwelling needle into the femoral artery under local anesthesia (metycaine), appropriate solutions for the measurement of inulin or mannitol and PAH clearances were infused into an arm vein. Then, under fluoroscopic control, a cardiac catheter was placed into the right renal vein and the location of the tip doubly checked by determining the renal PAH extraction, as previously described (2). Following three or four control urine collection periods, 2 ml. (80 mg. mercury) of a mercurial diuretic were injected intra-1 Supported in part by grants from the National Heart Institute, U. S. Public Health Service, Campbell Pharmaceutical Co., and the Martha M. Hall Foundation.2 Ei Lilly Research Fellow in Medicine.venously. To maintain a higher and better sustained plasma concentration of mercury, in three patients an additional 2 ml. of the mercurial were added to the inulin-PAH solution, which was infused at approximately 4 ml. per minute. Thiomerin, which has no theophylline component that might modify the excretion of mercury, was given to five of the patients while Mercuzanthin was given to the sixth. Previous studies (3) have established that the renal action of Thiomerin is qualitatively and quantitatively similar to that of other mercurial diuretics.Following the administration of the mercurial, periodic urine collections were continued at 15 to 20 minute intervals for the determination of renal clearances, and urinary electrolyte and mercury excretion. At appropriate intervals, simultaneous femoral arterial and renal venous blood samples were also collected for the determination of the renal extraction of inulin, PAH, and mercury. In one patient (W. M.), catheterization of the renal vein was not attempted.The determinations of inulin, mannitol, PAH and electrolytes were carried out by ...

The widespread use of mercurial diuretics has stimulated greater interest in the metabolism of organic mercurials in man. Recently proposed regimens (1) involving frequent, even daily, administration of mercurials, have focused particular attention on the 24 hour excretion of these compounds in relation to the cumulative toxicity of any mercury which may be retained. Moreover, little is known of the mechanism for eliminating mercury in the urine and its relation to the process of diuresis. Therefore, the following aspects of mercury excretion in man were studied: 1) the 24 hour urinary and fecal excretions of mercury after repeated administration of mercurial diuretics; 2) the course of urinary mercury excretion before, during and after the period of maximal diuretic response; 3) the effects on the excretion of mercury, water and electrolytes of pretreatment with substances known to modify the response to mercurial diuretics. MATERIALS AND METHODSThese studies were carried out on 17 patients, 13 of whom were in congestive heart failure. The latter were maintained on a restricted daily sodium intake of 8 to 10 meq. The non-cardiac subjects were on a regular hospital diet. Thiomerin was the mercurial generally employed, since it has no xanthine component which might independently influence the excretion of mercury while its tubular action is similar to that of other mercurials (2 Chemical analyses of urine or blood were performed by the following methods: sodium and potassium by means of a Perkin-Elmer 52A lithium internal standard flame photometer; chloride by a modification of Sendroy's iodometric method (3) ; total mercury by the dithizone method, as modified by Gettler and Lehman (4); creatinine by Peters' (5) modification of the Folin-Wu method. RESULTSA. Excretion of mercury. The results are illustrated in Figures I through 9 and Table I. From Figure 1, showing total urinary mercury excretion of 17 subjects, several facts are evident. 1) As a result of early, relatively rapid excretion of mercury, half of the total (2 ml. = 80 mg. mercury) dose appears in the urine within 2½ to three hours. Another 20 to 40 mg. is excreted within 18 to 24 hours. 2) There is a definite retardation in mercury excretion during the first few hours after subcutaneous, as compared with intravenous, injection. Subsequently, the difference in total mercury excretion between the two routes of administration disappears. 3) Pretreatment with ammonium chloride does not influence the rate or completeness of excretion of subcutaneously or intravenously administered mercurials.Despite the fairly complete urinary excretion of mercury within 20 to 24 hours, the output of 1208