The excretion of sodium by the kidney is influenced by changes in glomerular filtration rate (GFR), serum sodium concentration, adrenocortical activity, the quantity of nonreabsorbable solutes in the glomerular filtrate, and the volume of extracellular fluid (ECF) (1-4). Some of these factors alter sodium excretion by affecting the amount of sodium filtered; others modulate the tubular reabsorption of sodium.The mechanism whereby acute changes in the volume of ECF influence sodium excretion is not entirely clear. At least two factors, however, have been identified. Both the secretory rate of aldosterone and the GFR are influenced by alteration in the volume of ECF and may play important roles in the regulation of sodium excretion by volume. Alteration of sodium excretion by patients with Addison's disease in a parallel fashion with sodium intake and without detectable changes in GFR (5, 6) suggests that a third factor may be operative. Furthermore, a number of investigators (7-9) have shown that, under conditions where the volume of ECF was acutely altered in the face of fixed adrenocortical activity, sodium excretion varied independently of GFR, suggesting that changes in volume were in some manner influencing the tubular reabsorption of sodium independent of adrenocortical hormones.* Submitted for publication August 7, 1963; accepted October 31, 1963. This work was supported in part by U. S. Public Health Service grants HTS-5469 and 2A-5038. All, these studies, however, are open to the objection that errors in the measurements of GFR could lead to erroneous conclusions concerning the relative roles of filtration and tubular reabsorption (1, 10).Recently, de Wardener, Mills, Clapham, and Hayter (11) circumvented this difficulty by demonstrating that acute expansion of ECF volume with an infusion of isotonic saline increased sodium excretion despite both the administration of large doses of 9a-fluorohydrocortisone and marked reductions in GFR produced by aortic constriction. These results, which have subsequently been confirmed and extended by Levinsky and Lalone (12), establish that the increased sodium excretion after expansion of the ECF volume is the consequence of diminished tubular reabsorption of sodium via some mechanism other than suppression of adrenocortical activity. They do not, however, define the locus in the nephron wherein sodium reabsorption must have been suppressed.Our experiments were designed to localize within the nephron the site at which changes in ECF volume regulate sodium reabsorption. This we achieved by demonstrating that massive infusions of hypotonic saline increase sodium excretion under the following circumstances: 1) marked reduction in GFR produced by constriction of the aorta, 2) constant and maximal aldosterone activity achieved by injections of the hormone, and 3) maximal water diuresis. Under these conditions of maximal suppression of antidiuretic hormone (ADH), the amount of filtrate delivered to the diluting segment of the nephron can be roughly approximated from the ...

Under ordinary circumstances the elaboration of a dilute urine is dependent upon suppression of the secretion of antidiuretic hormone (ADH). Even when ADH secretion is maximally suppressed, however, a concentrated urine may be formed. Berliner The present experimiients were designied to examine the role of GFR, solute excretion, and sodium excretion on urinary tonicity when ADH activity is negligible. To determine whether acute reductions in GFR produce effects that are then obscured by adaptative changes, studies in which GFR was reduced for periods up to three months were also undertakeni. Materials and MethodsFemale mongrel dogs, weighing 10 to 17 kg and fed regular commercial diets, were used in all studies.The effects of acute and chronic reductions in GFR on the excretion of water and solutes were studied during water diuresis and during hypotonic saline diuresis.Acute reductions in GFR were produced in four dogs by inflating a balloon in the thoracic aorta. After the dogs were anesthetized with sodium pentobarbital, a balloon connected to an arterial catheter was inserted througlh the right brachial artery into the thoracic aorta to a point just above the renal arteries. Inflation of the balloon so that femoral arterial pressure was reduced byabout 50% reproducibly depressed GFR by about 30%.Urine was collected from an indwelling bladder catheter. Blood was collected with a Cournand needle in the femoral artery through which blood pressure was also monitored.The studies were then carried out in the following order (Table I)