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Although aldosterone has recently been shown to play a part in the retention of sodium by edematous subjects (5), the factors governing its production have not been defined.It has been reported (6) that sodium restriction in normal subjects leads to increases in urinary aldosterone-like steroids, and that the quantities of such steroids are, other things being equal, inversely proportional to the amount of sodium excreted in the urine (5). In the studies reported here we have confirmed these reports in part, and have sought to clarify the mechanism or mechanisms by which changes in sodium balance lead to changes in aldosterone secretion. The evidence supports the view that some function of extracellular fluid volume, and not sodium per se, mediates the regulation of aldosterone secretion by dietary sodium. METHODSStudies were done on 18 normal control subjects, on one patient with diabetes insipidus and on one with panhypopituitarism. They were maintained on metabolic regimen, in air-conditioned environment; intake of food and fluids was changed only as the design of experiment required changes of salt and water intake. In four instances, only water, dextrose and sodium chloride were given throughout the study. Body weight was determined daily under standard conditions, and blood drawn at the start of metabolic days. Urine was collected in 24-hour lots. Serum and urine were analyzed for sodium and potassium by flame photometer, with lithium as internal standard, for chloride by the method of Van Slyke and Hiller (7) and for osmolality by the instrument designed by Bowman, Trantham, and Caulfield (8) using as standards sodium chloride solutions corrected for "true" osmolality with the use of the In-

The presence of a sodium-retaining hormone, aldosterone, in the adrenal gland and adrenal venous blood (1-4), the increased urinary excretion of aldosterone during sodium depletion (5, 6) and the inability of men and animals with adrenal insufficiency to conserve sodium support the concept that the process by which the sodium content and thus the extracellular fluid (ECF) volume of the body are regulated includes adrenocortical control of sodium excretion by aldosterone secretion (7).That aldosterone is involved in the formation of edema is indicated by an increased urinary output of this hormone by patients with edema caused by heart failure, portal cirrhosis or nephrosis (8-13).The present work further defines the role of aldosterone in the control of ECF volume of normal men and in the formation of edema by patients with heart failure or portal cirrhosis. METHODSThe patients lived on a metabolic ward during the studies. Constant diets were prepared from uniform lots of food. The patients were weighed each morning after voiding and before breakfast. Blood samples were drawn 3 times a week before breakfast. Total collections of urine and feces were made. Urine was kept at 5°C. during and following collection. Sodium and potassium in diets, urine, feces and sera, and cation exchange resin in feces were determined as previously described (14 (Circulation, 1955, 12, 697).Sodium uptake is thus the percentage of the total exchange capacity of the resin occupied by sodium. The uptake of potassium by resin was calculated in the same fashion on the assumption that there were 10 mEq. of potassium per day uncombined with resin in the stool. The results are essentially the same if it is assumed that all of the sodium and potassium in the stool is combined with resin.

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Data are presented which support the concept that albumin enters the inner layer of the aortic wall by passage from the lumen of the aorta across the intimal endothelium. The rate of movement of albumin from serum into the aortic wall is much greater proximally where the aorta is wide than distally where it is narrow. Thus the rate correlates with the circumferential tension to which the aortic wall is subjected. The hypothesis is advanced that circumferential tension acts as n major determinant of transendothelial transfer of proteins into the aorta by widening the endothelial intercellular spaces through which the transfer occurs.T HE MOVEMENT of serum lipoproteins through arterial walls 1 is widely held to be of importance in the development of atherosclerosis. It thus appears of interest to study the movement of proteins in general into and out of arterial walls.Recently-we reported work in which data on the circulation of labeled albumin through the aortic wall of the rabbit were analyzed to yield numerical values for the rates of transfer of albumin into and out of that tissue. We are now reporting similar work on the thoracic aorta of the dog, the larger size of which makes possible investigation of the various layers of the wall at different levels along its length. The data support the concept that albumin enters the inner layer of the aortic wall by passage from the lumeu of the aorta across the intimal endothelium, and they demonstrate a progressive decrease in the rate of movement of albumin into the wall of the aorta from the origin of the aorta down to the diaphragm. A hypothesis based on the physical stresses in the aortic wall is presented to explain the progressive decrease in these rates.From the Clinic of General Medicine and Experimental Therapeutics of the National Heart Institute and the Biometrics Branch of the Division of Research Services, The Xational Institutes of Health, Bethesda, Md.Received for publication December 3, ]f);j8. METHODSHuman serum albumin labeled with radioactive iodine (RISA, Abbott) was dialyzed in cellophane tubing and then injected intravenously into a series of 27 dogs averaging 12 Kg. in weight. The dogs were killed at intervals following injection. Two were killed at 2 minutes, five at 10 minutes, four at 1.5 hours and at 3 hours, and three at 6 hours, at 18 hours, at 3 days, and at 6 days. The radioactivity of the serum and that fraction of the radioactivity which was dialyzable through cellophane, and the radioactivity of skin and of muscle from the chest wall, of Achilles' tendon, of sclera, of cornea, and of aorta, were determined with a well-type scintillation counter. The aorta from the valve ring to the braehiocephalic artery was separated into the outer side of the arch and the inner side of the arch. Each of these was split into an inner layer which contained intima and some media, a middle layer consisting of media, and an outer layer consisting of media and adventitia. The descending aorta below the left subelavian artery was separated into upper, mid...