The Natriuretic Hormones

The title follows from the original demonstration by Dr. Hugh de Wardener in 1961 that a humoral agent is produced after extracellular volume expansion which results in a vigorous diuresis and natriuresis. Thus the name of "natriuretic hormone" was coined. In the years that followed several investigators pursued the search for the hormone. What resulted, however, was the discovery of several hormones with different characteristics, all of which were natriuretic. Initially it was found that the hormone was similar in action to ouabain or digoxin, hence the appelation of ouabain-like or digoxin-like. The hormone was found to be an inhibitor of Na-K-ATPase, which would fit with it being a cardiotonic steroid. On the other hand, neither ouabain or digoxin migrated on Sephadex gel filtration in the same locus as the hormone. Other investigators claim to have identified the hormone-initially as a vanadium-diascorbate, later as bufadienolides such as marinobufagenin, yet later as a macrocylic derivative of inorganic carbon suboxide with a molecular weight of 408 Da. Some support for the latter finding was derived from an earlier report that a semi-purified Sephadex-derived compound was found to have a molecular weight of about 12,000 Da but the active compound, when split from its carrier protein, had a molecular weight of exactly 408 Da. This compound had not been further identified. As further development was the demonstration by Bricker and colleagues that a natriuretic substance could be purified from uremic urine. This turned out to be a xathurenic acid derivative. Meanwhile the focus began to turn to natriuretic peptides derived from heart (ANF and BNP). These peptides have a shorter duration of action than the cardiotonic steroid-like hormone and ANF has proved to be most useful as a measure of heart failure. It should also be stressed that marinobufagenin, like ANF, is elevated in congestive heart failure, whereas the steroid-like hormone is depressed or absent in this state. This review will attempt to describe and contrast the properties of each of the proposed natriuretic hormones, including their locus on Sephadex separation, potency, duration of action, chemical structure (if known), behavior in hypertension, renal failure, heart failure, and brain disease. As most recent work has focussed on marinobufagenin, this hormone will be brought up to date by investigators in the field

The Effect of Dialysates and Ultrafiltrates of Plasma of Saline-Loaded Dogs on Toad Bladder Sodium Transport

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