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.

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

MEYER, PHILIPPE, JOEL MENARD, NIC~LAS PAPANICOLAOU, JEAN-M. ALEXANDRE$LAUDINE DEVAUX,AND PAUL MILLIEZ. Mechanism of renin release following furosemide diuresis in rabbit. Am. J. Physiol. 215(4) : 908-915. 1968.-Injection of furosemide (10 mg/kg, iv) into rabbits increased plasma renin activity within 7 min; plasma renin activity increased further throughout the course of the experiment and rvas associated with a moderate reduction of blood pressure, of plasma sodium concentration, and a marked contraction of plasma volume. A concomitant increase of extracellular fluid with isotonic saline infusion or of plasma volume with infusion of salt-poor albumin reduced the furosemide-induced renin secretion. Prevention of urinary losses by shunting urine into the femoral vein did not alter the furosemide-induced renin secretion despite the constancy of blood pressure, plasma sodium concentration, and plasma volume; the rise of plasma renin activity was, however, prevented when extracellular or plasma volume expansion was combined with reinfusion of urine. There was no specific relationship between changes in GFR and in plasma renin activity, although the data suggest a possible inverse correlation in the extreme upper ranges of both parameters. It is concluded that: a) furosemide-induced renin release is induced by some intrarenal mechanism, possibly by the increase of intratubular sodium concentration, b) plasma or extracellular fluid expansion counteracts the renin-stimulating effect of furosemide, and c) the renin-angiotensin system may have a regulating effect on glomerular filtration rate.

Mechanism of renin release following furosemide diuresis in rabbit.

Decreased arterial Na+ -K+ pump and cardiac Na+, K-+ ATPase activities have now been demonstrated in several types of experimental volume expanded hypertension The changes are not secondary to elevated pressure since they also occur in veins and right ventricle where the pressure is not elevated Decreased arterial Na+ K+ pump activity can be reproduced by acute volume expansion of the normal rat and plasma extracts from this rat suppress pump activity when applied to arteries from another rat Suppression of Na+ -K+ pump activity in arteries, veins and heart, with ouabain for example, leads to increased contractile activity Thus the volume expansion, reduced pump activity, and hypertension appear to be causally related through an ouabain-like humoral agent Certain other evidence suggests that the pump defect extends to the sympathetic nerve endings, thereby reducing the efficiency of neural compensatory mechanisms

The sodium-potassium pump in volume expanded hypertension.

Physical Factors IN recent years numerous investigations have demonstrated effects on urinary sodium excretion of so-called "physical factors" that are independent of glomerular filtration rate and...

Tubular reabsorption of sodium ion: influence of factors other than aldosterone and glomerular filtration rate. 2.

An inhibitor of transepithelial sodium transport was found in a low molecular weight fraction obtained from serum of patients with far advanced chronic renal disease. In 18 nondialyzed patients, the mean inhibition of short circuit current (SCC) was 24.9 +/-2.2% (SE). With a comparable fraction from 11 normal subjects. SCC decreased by only 5.3 +/-1.5%. There was significantly greater inhibition with the serum fractions of patients with end stage renal disease being maintained on chronic hemodialysis than in the normal control group; but the degree of inhibition in the dialyzed population was significantly less than that observed in the nondialyzed chronically uremic patients. The inhibition of SCC produced by the serum fractions of a group of seven patients with acute renal failure was not significantly different from the control group despite the presence of high grade uremia in the former. The inhibitory fraction has characteristics identical with the uremic serum fraction which previously has been shown to inhibit p-aminohippurate (PAH) uptake by rabbit kidney cortical slices. With gel filtration through Sephadex G-25, the active fraction appears after the major peaks of substances as small as urea and sodium; hence it may have been retarded on the column. But its ultrafiltration characteristics suggest that its molecular weight may be less than 1000. The inhibitory capability was not destroyed by boiling, freezing, or digestion with chymotrypsin or pronase. Neither methylguanidine nor guanidinosuccinic acid in concentrations well above those present in the serum of uremic patients inhibited sodium transport in the frog skin. The data suggest that there is an inhibitor of sodium transport in the serum of patients with chronic uremia. The role of this material in the regulation of sodium excretion in uremia as well as its possible role as a uremic toxin are subjects of both theoretical and practical interest.

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V. Pliska

Papers

The chemical nature and tissue source of natriuretic hormone

The cow as a model for investigating natriuretic activity.

Natriuretic and Antinatriferic Activities in Deproteinised Bovine Plasma after Dextran Infusion