The effect of dialysates and ultrafiltrates of plasma of saline-loaded dogs on toad bladder sodium transport

Abstract

A B S T R A C T In order to obtain direct evidence for the existence of a natriuretic hormone, dialysates and ultrafiltrates of plasma of dogs expanded with saline were tested for effects on sodium transport by the toad urinary bladder. Dialysate was obtained by dialysis of blood in vivo in a clinical dialyzer and by dialysis in vitro of small volumes of blood using a miniature model of the clinical dialyzer. Ultrafiltrates were prepared using selective molecular filters which permit passage of substances on the basis of molecular weight and three dimensional configuration.Dialysates and ultrafiltrates of hydropenic dogs caused a change in toad bladder potential difference of + 1% and in short circuit current of -5%. In contrast, dialysates and ultrafiltrates from expanded dogs caused a change in potential difference of -23% and in short circuit current of -32%, a highly significant difference. Onset of reduction of short circuit current occurred within 3-5 min, reaching a maximum in 10-20 min. The effect was rapidly reversible, was specific for the serosal surface of the bladder, and could not be explained on the basis of nonspecific alterations in ionic composition or by dilutional effects. Ultrafiltrates of jugular vein plasma caused significantly more reduction of short circuit current than ultrafiltrates of femoral vein plasma. The data indicate the presence in plasma of saline-loaded dogs of a dialyzable inhibitor of toad bladder sodium transport. Ultrafiltrate studies using membranes of appropriate selectivity suggest the factor has a molecular weight of less than 3000.

Evidence for a Humoral Mechanism in Volume Expansion Natriuresis

“…In several studies (8,13,14), the natriuresis paralleled an increase in renal blood flow and glomerular filtration rate suggesting that the factor promoted a natriuresis through a vasodilating effect on the kidney. However, this conclusion is difficult to reconcile with those studies purporting to show a direct effect of this factor on sodium transport in isolated membranes (2,3,5) or tubule fragments (4,7).…”

“…laboratories (1)(2)(3)(4)(5)(6)(7) have reported the presence of a factor in blood or urine which exhibits natriuretic activity when tested in various biological assay systems, it remains to be established that this factor plays a physiologic role in regulating sodium excretion in the intact animal.…”

An inhibitor of sodium transport in the urine of dogs with normal renal function.

“…Finally, and most critically, the presence of the inhibitor in the urine of patients and dogs with chronic uremia and of the present dogs with normal renal function appears to correlate with the dictates of maintaining external sodium balance. A number of other investigators have now demonstrated the presence of natriuretic factor(s) or inhibitor(s) of sodium transport in the blood of animals and man using whole animal experiments (13)(14)(15)(16)(17)(18)(19)(20)(21) or in vitro assays (13,18,20,(22)(23)(24)(25)(26)(27)(28)(29). Similarly, extracts of urine have also been shown to contain natriuretic substance(s) (16,17,19,20,(30)(31)(32)(33)(34)(35)(36) or inhibitor(s) of sodium transport (20,37,38).…”

Sodium transport inhibitor from bovine hypothalamus.

“…Physiologic studies provided considerable evidence for existence of such a "third factor" capable of modulating urinary sodium excretion independently of filtered sodium load and mineralocorticoid activity (2)(3)(4). Assays in vitro of plasma and urine extracts from subjects and animals with expanded extracellular fluid volume (5,6), certain chronic uremic patients (7), and animals in mineralocorticoid "escape" (8) confirmed the biological effect of sodium transport inhibition across living cell membranes. Several investigators (9)(10)(11) have provided experimental evidence supporting the view that the brain is the source of the natriuretic factor(s).…”