Natriuretic effect of digoxin-like immunoreactive substance on dog kidney

We previously reported that digoxin-like immunoreactive substance (DLIS) was found only in the blood of those dialysis patients who were hypertensive and had high systemic vascular resistance. In order to determine whether the DLIS was a marker for the natriuretic hormone, renal infusion studies were carried out in anesthetized dogs. When ultrafiltrates from patients with high blood DLIS levels were infused into the renal artery of one kidney there was a significant increase in the fractional excretion of sodium (FE Na) from its baseline value. Further, the FE Na of these kidneys were significantly higher than the FE Na noted for the contralateral kidneys which were simultaneously infused with ultrafiltrates obtained from dialysis patients lacking DLIS activity in their blood. We conclude that the DLIS is or represents a marker for natriuretic hormone. Since the natriuresis noted was independent of renal plasma flow and glomerular filtration rate and since the fractional excretion of potassium was not influenced by the infusion, we believe that DLIS is different from atrial natriuretic factor.     

Antidiuretic Effect of Eel ANP Infused at Physiological Doses in Conscious, Seawater-Adapted Eels, Anguilla japonica

Atrial natriuretic peptide (ANP) is known as a potent natriuretic/diuretic hormone in vertebrates. However, eel ANP infused at doses that did not alter arterial blood pressure (0.3-3.0 pmol/kg/min) decreased urine volume and increased urinary Na concentration in seawater (SW)-adapted eels but not in freshwater (FW)-adapted eels. The renal effects were dose-dependent and disappeared after infusate was switched back to a vehicle (0.9% NaCl). Urinary Na excretion (volume x Na concentration) did not change during ANP infusion. ANP infusion increased plasma ANP concentration, but the increase at the highest dose was still within those observed endogenously after injection of hypertonic saline. Urinary Mg and Ca concentrations increased during ANP infusion in SW eels, but urinary Ca excretion decreased in FW eels. Plasma Na concentration profoundly decreased during ANP infusion only in SW eels, suggesting that ANP stimulates Na extrusion via non-renal routes. These results indicate that ANP is a hormone which specifically extrudes Na ions and thereby promotes SW adaptation in the eel. This is in sharp contrast with mammals where ANP is a volume regulating hormone that extrudes both Na and water.     

Effects of atrial natriuretic factor on renal function and cyclic GMP production

Anesthetized beagle dogs received increasing doses of continuous infusions of a 26-amino-acid synthetic atrial natriuretic factor (ANF). Urinary sodium excretion rose in a dose-dependent manner to a maximum level similar to that seen after hydrochlorothiazide administration. Mean arterial blood pressure decreased, but only modestly, and not in a dose-dependent fashion. Dogs chronically retaining NaCl secondary to constriction of the thoracic inferior vena cava showed only modestly enhanced natriuresis when infused with similar levels of ANF. When ANF was infused directly into the renal artery of anesthetized beagles, a dose-dependent natriuresis and calciuresis were observed with maximal fractional sodium excretion averaging approximately 8%. Although glomerular filtration tended to increase, the average dose-related changes were not significant. Cyclic GMP excretion was increased during intra-renal-arterial infusion of ANF. Excretion of cyclic GMP by both the infused and noninfused kidneys was equal, which suggests that urinary cyclic GMP was not nephrogenous but derived from the elevated circulating levels. These and other data from rats dissociate changes in urinary cyclic GMP excretion and sodium excretion.     

A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis.

The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12 +/- 15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point (10, 20, 30, 60, 120 min after drinking onset), and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion. These data suggest that acute ethanol administration causes a rapid increase in plasma levels of atrial natriuretic peptide, which could be an important factor of ethanol-induced diuresis. The main mechanisms for increased atrial natriuretic peptide release from atria after acute ethanol ingestion seem to be atrial stretch, due to the increase in arterial blood pressure, in heart rate, in sympathetic tone, and in plasma osmolality, and to a direct secretory effect by antidiuretic hormone.     

The natriuretic peptide system in eels: a key endocrine system for euryhalinity?

The natriuretic peptide system of a euryhaline teleost, the Japanese eel (Anguilla japonica), consists of three types of hormones [atrial natriuretic peptide (ANP), ventricular natriuretic peptide (VNP), and C-type natriuretic peptide (CNP)] and four types of receptors [natriuretic peptide receptors (NPR)-A, -B, -C, and -D]. Although ANP is recognized as a volume-regulating hormone that extrudes both Na(+) and water in mammals, ANP more specifically extrudes Na(+) in eels. Accumulating evidence shows that ANP is secreted in response to hypernatremia and acts to inhibit the uptake and to stimulate the excretion of Na(+) but not water, thereby promoting seawater (SW) adaptation. In fact, ANP is secreted immediately after transfer of eels to SW and ameliorates sudden increases in plasma Na(+) concentration through inhibition of drinking and intestinal absorption of NaCl. ANP also stimulates the secretion of cortisol, a long-acting hormone for SW adaptation, whereas ANP itself disappears quickly from the circulation. Thus ANP is a primary hormone responsible for the initial phase of SW adaptation. By contrast, CNP appears to be a hormone involved in freshwater (FW) adaptation. Recent data show that the gene expression of CNP and its specific receptor, NPR-B, is much enhanced in FW eels. In fact, CNP infusion increases (22)Na uptake from the environment in FW eels. These results show that ANP and CNP, despite high sequence identity, have opposite effects on salinity adaptation in eels. This difference apparently originates from the difference in their specific receptors, ANP for NPR-A and CNP for NPR-B. VNP may compensate the effects of ANP and CNP for adaptation to respective media, because it has high affinity to both receptors. On the basis of these data, the authors suggest that the natriuretic peptide system is a key endocrine system that allows this euryhaline fish to adapt to diverse osmotic environments, particularly in the initial phase of adaptation.     

Cerebral osmoregulation of renal sodium excretion--a response analogous to thirst and vasopressin release

Studies in sheep have shown that renal excretion of sodium may be under osmoregulatory control. When sheep become dehydrated, or are infused intravenously with hypertonic saline, they increase renal Na excretion in addition to secreting vasopressin and developing a thirst. These natriuretic, antidiuretic, and dipsogenic responses to dehydration and hypertonicity can be greatly reduced by lowering the cerebrospinal fluid NaCl concentration or by prior ablation of tissue in the anterior wall of the third ventricle. Lowering of cerebrospinal fluid NaCl concentration also prevents postprandial natriuresis which normally occurs in association with a postprandial increase in plasma Na concentration and tonicity. We propose that there is a cerebral osmoregulatory control of Na excretion which may interact with volume influences from the cardiovascular system to regulate renal Na output. The effector mechanism from brain to kidney mediating such cerebral control of Na excretion is probably hormonal.     

The possible role of endogenous digitalis-like substance in the regulation of circadian changes in urinary electrolyte excretion in man

The urinary volume (U.V.), Na excretion (UNaV) and K excretion (UKV) have been reported to show a circadian rhythm in man, but the mechanism of this rhythm has not been made clear. To investigate how atrial natriuretic peptide (ANP) and endogenous digitalis-like substance (DLS) participate in the circadian change in urinary electrolyte, the circadian changes in ANP and DLS (digoxin-like immunoactivity: DLI, Na-K-ATPase inhibitor: ATPI, ouabain binding inhibitor to Na-K-ATPase: OBI) were evaluated in 5 normal man. ANP, DLI and OBI showed no significant correlation with urinary electrolyte excretion, but there was a significant positive correlation between plasma ATPI and urinary Na excretion. From these results it is suggested that circulating Na-K-ATPase inhibitor (plasma ATPI) may be involved in the regulation of the circadian rhythm of urinary Na excretion.     

Atrial natriuretic factor inhibits vasopressin secretion in conscious sheep

To test the hypothesis that atrial natriuretic factor (ANF) has a centrally mediated action on body fluid homeostasis, the effects of intracerebroventricularly (ICV) infused ANF on plasma vasopressin (AVP) concentration and urinary water and electrolyte excretion were investigated in euhydrated and water-deprived conscious sheep. ICV ANF decreased plasma AVP concentration and increased urinary free water excretion in euhydrated sheep, with excretion of Na and K unaltered. However, ICV ANF did not affect urinary volume, free water clearance, or excretion of Na and K in dehydrated animals, although plasma AVP concentration was significantly decreased. The relationship between urine volume and plasma AVP concentration was fitted by a power curve: urine volume = 0.79 X [AVP]-0.71; urine volume changes very little as a function of AVP concentration at the higher ranges. Intravenous infusion of the same amount of ANF was without effect on plasma AVP concentration or urinary excretion in both euhydrated and dehydrated animals. Mean arterial pressure was unchanged throughout all experiments. These results are consistent with the hypothesis that central ANF inhibits AVP secretion.     

Vasoactive humoral systems and sodium transport in erythrocytes of normotensive offsprings of essential hypertensive subjects

Urinary excretion of sodium, potassium and some hormones influencing their transport was investigated before and after i.v. furosemide administration in 10 offsprings of normotensive subjects who had a normal Na(+)-K+ cotransport activity and in 26 normotensive men with a positive family history of essential hypertension. The latter group was divided into two subgroups with regard to the activity of red cell Na(+)-K+ cotransport. The Co[-] subjects with a decreased Na(+)-K+ cotransport activity had lower urinary excretion of sodium and vasodilators (kallikrein, dopamine, PGE2 and prostacyclin) after furosemide administration. The urinary excretion of vasopressor factors (PGF2 alpha, thromboxane) was unchanged as compared with that in the control group. There was a significant correlation between Na(+)-K+ cotransport activity and kallikrein excretion. These results suggest a deficit in the secretion of renal substances with vasodilating or natriuretic effects in Co[-] subjects. This could negatively affect their sodium excretion.     

The effect of suppression of prostaglandin synthesis on renal function in rats with intact and reduced renal mass

The present study was undertaken to assess the role of prostaglandin system in the compensatory response to reduced nephron population, respective to renal function and electrolyte excretion. Intact and nephrectomized rats were divided in 4 groups: 1) rats pretreated with indomethacin, 2) rats pretreated with the vehicle of indomethacin, 3) rats pretreated with sulindac, and 4) rats pretreated with the vehicle of sulindac.In normal rats, indomethacin administration resulted in a mild decrease in creatinine clearance and a significant reduction of the urinary Na excretion. In the rats with reduced renal mass treated with indomethacin, the creatinine clearance did not differ from that in the control group. The 24 h urinary sodium excretion and the fractional excretion of sodium, however, were significantly lower in the indomethacin treated animals than in the control rats. No change in the creatinine clearance or in the sodium excretion was observed in all groups pretreated with sulindac.The urinary PGE₂ and thromboxane excretion was significantly lower in the indomethacin treated intact rats and the rats with reduced renal mass. Sulindac induced a slight decrease in urinary excretion of PGE₂ in intact rats. No significant change in urinary excretion of PGE₂ or thromboxane was seen after sulindac in the rats with reduced renal mass.The antinatriuretic effect of indomethacin was dissociated from changes in urine flow in all groups of animals, suggesting that the increase in Na reabsorption tool place in a water impermeable segment of nephron.These results suggest that the compensatory increase in urinary Na excretion per nephron in rats with reduced nephron population at least partly depends on an intact prostaglandin synthesis.     

Synthesis and renal function study of Val-Asp-[Arg8]-vasopressin

A new neurohypophyseal hormone analogue, Val-Asp-[Arg⁸]-vasopressin (VAAVP), was synthesized by the stepwise solution techniques and its effect on systemic blood pressure and renal function was examined in nondiuretic Sprague-Dawley rats. Clearance of inulin was used to study glomerular filtration rate. Intravenous administration of 50 pmole/100g. b. wt. VAAVP caused diuresis and increase in urinary excretion of sodium and potassium without significant change of mean arterial blood pressure. The same dose of VAAVP caused a maximal increase infractional excretion of sodium by 80% although it also caused a slight increase of GFR. The present study suggests that VAAVP could be a natriuretic hormone which acts directly on kidney without affecting systemic circulation.     

Zinc deficiency inhibits the direct growth effect of growth hormone on the tibia of hypophysectomized rats

The effect of zinc deficiency on the direct-growth effect of growth hormone (GH) on tibia growth in hypophysectomized rats was studied. There were three dietary groups. Zinc deficient (ZD) group (0.9 mg/kg diet), control (C) group (66 mg/kg diet) and zinc adequate pair fed (PF) group (66 mg zinc/kg diet). All rats in each group received local infusion of recombinant human-growth hormone (hGH) (1 Μg/d), except for half of the animals in the control group, which were sham-treated, receiving vehicle infusion only. The substances were infused continuously for 13 d by osmotic minipumps through a catheter implanted into the right femoral artery. Food intake was lower and body weight loss was greater in ZD, and PF animals compared with C animals (p < 0.001). Tissuezinc concentration and plasma alkaline-phosphatase activity were decreased (p < 0.05) by dietary-zinc deficiency. GH infusion increased the tibial-epiphyseal width of the treated right limb, but not of the noninfused left limb in C and PF animals. However, in ZD rats, no difference was found between the infused and the noninfused limbs. These results demonstrate that zinc deficiency inhibits the direct-growth effect of GH on long-bone growth.     

大鼠脑室内注射ANGⅡ和ANGⅡ抗体对尿钠排出和肾皮质...

In anesthetized rats, it was observed that intracerebroventricular (I.C.V.) microinjection of angiotensin II (ANG II) in a dose of 16 pg evoked a significant increase in renal sodium excretion which began within 15 min and lasted for 90 min. The activity of Na+.K(+)-ATPase in renal cortex after I.C.V. microinjection of ANG II (1.51 +/- 0.26 mumol Pi/mg Pro.h) was inhibited as compared with that of the control injecting of artificial cerebrospinal fluid (2.66 +/- 0.28 mumol Pi/mg Pro.h, P less than 0.01). There was no change in mean arterial pressure. Within 15 min after I.C.V. administration of ANG II antibody, however, and antinatriuretic period of 135 min and a higher activity of Na+.K(+)-ATPase in renal cortex (3.61 +/- 0.34 mumol Pi/mg Pro.h, P less than 0.05 compared with control) were observed. There was no natriuresis in the animals microinjected with ANG II either into femoral vein or into spinal subarachnoid space. The result of the present investigation suggests that brain endogenous ANG II may possess some natriuretic activity possibly through inhibiting renal Na+.K(+)-ATPase activity.     

Leptin decreases renal medullary Na(+), K(+)-ATPase activity through phosphatidylinositol 3-kinase dependent mechanism.

We examined the effect of leptin on renal function and renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPase activities in the rat. Leptin was infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. Leptin infused at doses of 1 and 10 microg/kg/min increased urine output by 40% and 140%, respectively. Urinary Na(+) excretion increased in rats receiving leptin at doses of 0.1, 1, and 10 microg/kg/min by 57.6%, 124.2% and 163.6%, respectively. Leptin had no effect on creatinine clearance, potassium excretion and phosphate excretion. Na(+),K(+)-ATPase activity in the renal medulla of rats treated with 1 and 10 microg/kg/min leptin was lower than in control animals by 25.5% and 33.2%, respectively. In contrast, cortical Na(+),K(+)-ATPase as well as either cortical or medullary ouabain-sensitive H(+),K(+)-ATPase activities did not differ between leptin-treated and control animals. The effect of leptin on Na(+),K(+)-ATPase activity was abolished by actin depolymerizing agents, cytochalazin D and latrunculin B, and by phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002. These results indicate that: 1). natriuretic effect of leptin is mediated, at least in part, by decrease in renal medullary Na(+),K(+)-ATPase activity, 2). inhibition of medullary Na(+),K(+)-ATPase by leptin is mediated by PI3K and requires integrity of actin cytoskeleton.     

Role of natriuretic factor in central nervous system (CNS)-induced natriuresis

The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.     

Effect of vasoactive substances on natriuresis induced by atrial natriuretic peptide in isolated perfused rat kidneys

We studied the interaction between synthetic atrial natriuretic peptide (ANP) and various vasoactive substances, which included isoproterenol (ISO), aminophylline (AMI), and dibutyryl cyclic AMP (dBcAMP) as vasodilators, and angiotensin II (AII) and norepinephrine (NE) as vasoconstrictors, and prazosin as an alpha-blocker in isolated perfused rat kidneys (IPK). When 10(-9) mol of ANP was administered in 75 ml of a perfusate, the renal vascular resistance (RVR) was transiently decreased for 5 min, and increased thereafter. Simultaneously, ANP increased the glomerular filtration rate (GFR), urine flow (UV), absolute Na excretion (UNaV) and absolute K excretion (UKV). All of the above mentioned effects of ANP were significantly inhibited by administering ISO, AMI or dBcAMP. On the other hand, the administration of AII and NE significantly enhanced the increases in UV and UNaV and the fractional excretion of Na induced by ANP, although AII and NE had no influence on the changes in RVR and GFR induced by ANP. Prazosin did not modify the renal effects of ANP. These results suggest that the natriuretic effect of ANP is inhibited by agents that increase cyclic AMP in vascular smooth muscle cells. It is also suggested that the natriuretic effects of ANP can be explained by an increase in GFR and changes in intrarenal hemodynamics, rather than by the direct effect of ANP on renal tubules.     

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.     

The effect of environmental hypercapnia and salinity on the expression of NHE-like isoforms in the gills of a euryhaline fish (Fundulus heteroclitus)

The current models for branchial acid excretion in fishes include Na(+)/H(+) exchange and the electrogenic excretion of H+ via H+-ATPase. The predominant route of acid excretion in some freshwater fishes is thought to be via the H+-ATPase/Na+ channel system. The euryhaline Fundulus heteroclitus may not fit this profile even when adapted to freshwater (FW). We hypothesize that the Na+/H+ exchanger (NHE) in this species may play a predominant role in acid-base regulation for both marine and FW adapted animals. Acidosis induced by ambient hypercapnia (1% CO2 in air), resulted in an increase in net H+ excretion to the water in F. heteroclitus pre-adapted to FW, brackish (isoosmotic; BW) and seawater (SW). Both FW and SW adapted mummichogs were tested for NHE protein expression using mammalian NHE antibodies, and we identified NHE-like immunoreactive proteins in gill membrane preparations from both groups. Hypercapnia induced a approximately three-fold elevation in gill NHE2-like protein in FW animals but SW adapted fish showed inconsistent NHE3-like protein expression. There was no change in NHE-1 levels in FW fish. In contrast, SW animals demonstrated a significant increase in both NHE1 and NHE3-like proteins following hypercapnia but limited expression of the NHE2 protein. We hypothesize that different isoforms of NHE may be preferentially expressed depending on the salinity to which the animals are adapted. Net H+ transfers during acidosis may be driven, at least in part by the action of these transporters.     

Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA–salt hypertensive rats

Although deoxycorticosterone acetate (DOCA)–salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA–salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of α-1 subunit of Na,K–ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA–salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.     

Influence of augmentation of excretory renal mass on renal function after alpha-receptor blockade

The effect of renal function of an augmentation of the excretory renal mass was investigated in 10 dogs without drug treatment and in 10 animals with alpha-receptor blockade. In the untreated group, augmentation of excretory renal mass by transplantation into the neck of one pair of kidneys isolated from another animal caused the following changes in the kidneys in situ: marked elevation in CPAH, slight decrease in Cinulin, slight diminution of urine excretion and a pronounced fall in sodium excretion. The amount of urine and sodium excreted by the four kidneys was identical with that previously excreted by the two kidneys in situ. In animals with alpha-receptor blockade, augmentation of the excretory renal mass had the following consequences in the in situ kidneys, CPAH, and Cinulin remained unchanged while urine and sodium excretion decreased to the same extent as in the untreated control group. The amount of urine and of sodium excreted by the four kidneys was the same as that excreted by the kidneys in situ, prior to transplantation of isolated kidneys, i.e. before the augmentation of excretory renal mass. It seems that the decrease in sodium excretion of the kidneys in situ was not due to the haemodynamic changes evoked by the load on the circulation; it was rather consequence of some quick, presumably humoral, regulation. The diminution of sodium excretion in the kidneys in situ after augmentation of the excretory renal mass has been ascribed to an increased utilization by the four kidneys of the natriuretic factor(s), i.e. to a diminution in the plasma level of the natriuretic hormone.