Previous studies have shown that it is possible to extract a natriuretic factor from the renal tissue of rats. This substance, which can be isolated by fractionation through a G-25 Sephadex column, shows a strong correlation with sodium elimination by the kidney. The present work was designed to compare the effects of expansion by a Ringer's solution versus an albumin solution on the presence of this factor and the natriuretic response in the rat. Albumin-expanded rats, like control nonexpanded rats, which have no natriuretic response, do not exhibit any active natriuretic factor in their kidneys. In contrast, significant activity of the natriuretic factor is found in the kidneys of Ringer-expanded rats, which also respond by a significant natriuresis (P less than 0.001). We conclude that the expansion of the extracellular fluid volume, as opposed to the expansion of the intravascular volume, only determines both the presence of the natriuretic factor and the physiologic natriuretic response. As the difference in the sodium transport by the renal tubule in these two modes of expansion takes place in the collecting duct, we suggest that the natriuretic factor acts at this level.

A previously described natriuretic factor found in urine from man and dogs receiving a high salt diet has been postulated to be of hormonal nature. In order to test this hypothesis, natriuretic factor obtained from a pool of human urine of a standard activity has been injected into rats fed 0.55 (group A), 3.55 (group B), 6.55 (group C) mEq sodium a day as it has been shown that the endogenous activity of this factor depends on the sodium content of the diet. This material induces an increment of the UNaV and FENa in the rats averaging respectively 429.6 +/- 150.1% and 317.5 +/- 71.14% for the rats from group A, 103 +/- 29% and 99.7 +/- 26.25% for the rats from group B, 56.3 +/- 34.4% and 63.2 +/- 35.8% for the rats from group C reflecting the degree of statistical significance observed between the absolute values obtained during the control and experimental periods for each group. In addition, a dose-response curve has been established. Altogether the results suggest the hormonal nature of the natriuretic factor and design the kidney as the target organ. These data allow to define the best conditions under which the rats have to be in order to provide a valuable bioassay for this natriuretic material.

1. The effect of the sodium content of the diet on the natriuretic activity of an extract from the kidneys was studied in non-expanded and volume-expanded rats. 2. The kidney tissue was homogenized and the supernatant fractionated by gel filtration of Sephadex G-25. A single low-molecular-weight fraction eluted after the salt possessed the natriuretic activity and was tested on a rat bioassay. 3. The natriuretic activity of the fraction obtained from the kidneys of non-expanded rats was related to the sodium intake. 4. After an acute extracellular volume expansion, the natriuretic activity obtained from the fraction extracted from the kidneys was much greater than before expansion and was related to the dietary intake of sodium.