Plasma Saluretic Activity: Its Nature and Relation to Oxytocin Analogs

149

A B s T R A C T The present study was designed to examine the question of whether or not there is a natriuretic hormonal substance involved in the renal regulation of sodium balance.For this purpose, procedures for concentration and fractionation of plasma and urine samples and a sensitive bioassay for demonstrating changes in renal sodium excretion were developed. The natriuretic assay utilized rats with mild diabetes insipidus which were maintained in salt and water balance.Using these approaches a natriuretic humoral substance was demonstrated in plasma and urine from normal man and sheep, and in patients with primary aldosteronism or essential hypertension.It seems likely that this substance participates in day to day regulation of sodium balance because it was not detectable in sodium-depleted subjects and it consistently appeared in the sodium-loaded subjects.The hormonal agent may not act immediately and its activity can be apparent for up to 3 hr. Full expression of its activity requires that the assay animals be appropriately volume expanded. This suggests that the increases in sodium excretion mediated by this hormonal substance depend in part on the coparticipation of other physical and perhaps humoral factors.This natriuretic substance appears to be of large molecular weight or carried by a large molecule. The data suggest that it acts, at least in part, to block sodium reabsorption in a more distal portion of the tubule.

Section: Discussionmentioning

confidence: 89%

Natriuretic activity in plasma and urine of salt-loaded man and sheep

Je¹,

Jd²,

Jh³

1969

149

“…After the infusion of the control fraction, there was no significant change in any of the parameters. Immediately after infusion of the expanded fraction IV there was an increase in V from 10 and in FENa from 1.29 to 5.22%; GFR remained constant. The increase in UN.V persisted for 120 min before returning to base-line values.…”

Section: Resultsmentioning

confidence: 96%

A natriuretic principle derived from kidney tissue of volume-expanded rats

Gonick¹,

Saldanha²

1975

A S T R A CT Homogenates of kidneys from hydropenic and volume-expanded rats were subjected to gel filtration with Sephadex G-25. A fraction of the eluate coincident with the fourth UV peak was injected into the aorta of rats with one kidney excluded. A fraction eluting before the albumin peak was utilized as a control. Significant natriuresis and diuresis were observed after infusion of the fraction obtained from volumeexpanded kidneys but not after infusion of the fraction from hvdropenic kidneys or the control fraction.

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Favre¹,

Hwang²,

Schmidt³

et al. 1975

AB STRA CT The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a sodium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq sodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P < 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P <0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog.