Increase in plasma sodium enhances natriuresis in response to a sodium load unable to change plasma atrial peptide concentration

The influence of plasma sodium concentration in the control of sodium excretion was investigated in conscious, water-diuretic dogs. NaCl was infused for 60 min as a hypertonic or isotonic solution at a rate of 60 mumol NaCl min-1 kg-1 body wt. Plasma sodium concentration rose only during hypertonic infusion (P less than 0.05). Sodium excretion increased markedly with both infusions (hypertonic, from 2.4 +/- 0.6 to 105 +/- 27 mumol min-1; isotonic, from 3.9 +/- 1.3 to 58 +/- 17 mumol min-1). Fractional sodium excretion increased more during hypertonic than during isotonic infusion. Hypertonic infusion decreased diuresis from 3.1 +/- 0.5 to 1.3 +/- 0.6 ml min-1, while isotonic infusion elicited an increase from 3.9 +/- 0.5 to 7.2 +/- 0.7 ml min-1. Plasma renin activity and plasma aldosterone decreased markedly in both series (P less than 0.05), the relative changes in the two series being very similar. Central venous pressure increased (2.8 +/- 0.7 to 4.5 +/- 1.0 mmHg) during isotonic infusion but not significantly during hypertonic infusion. Arterial pressure, heart rate and plasma levels of atrial natriuretic peptide and catecholamines did not change measurably in either series. It is concluded that simultaneous increases in extracellular volume and sodium concentration cause a larger natriuretic response than a change in volume alone, and that a 40-fold increase in sodium excretion may occur without measurable changes in plasma atrial natriuretic peptide concentration.     

Isotonic and hypertonic sodium loading in supine humans

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day^–1. Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L^–1). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 ± 0.3 mmol L^–1). Oncotic pressure decreased significantly more with isotonic saline (4.1 ± 0.3 mmHg) than with hypertonic saline (3.2 ± 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 ± 13 mmol) and hypertonic saline (123 ± 10 mmol) were statistically identical exceeding that of time control (81 ± 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.     

Isotonic and hypertonic sodium loading in supine humans.

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day(-1). Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L(-1)). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 +/- 0.3 mmol L(-1)). Oncotic pressure decreased significantly more with isotonic saline (4.1 +/- 0.3 mmHg) than with hypertonic saline (3.2 +/- 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 +/- 13 mmol) and hypertonic saline (123 +/- 10 mmol) were statistically identical exceeding that of time control (81 +/- 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.     

Serum uric acid level and fractional excretion of urate in fluid and electrolyte disturbances]

Changes in renal urate clearance may reflect altered glomerular dynamics more precisely than other commonly used indices. Extracellular fluid volume expansion is known to be correlated with uricosuria, while volume depletion is associated with decreased urate excretion. The diagnostic usefulness of measuring serum urate levels and fractional excretions of urate in SIADH, incipient diabetic nephropathy, and prerenal azotemia have been reviewed. In SIADH, profound hypouricemia and markedly increased fractional excretion of urate (FEUA) accompany the extracellular fluid volume expansion. In prerenal azotemia, decreased FEUA may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure. In incipient diabetic nephropathy, glomerular hyperfiltration may increase renal urate clearance and lower the serum uric acid level. Hypouricemia may also predict the future progression of incipient nephropathy in type II diabetes.     

A comparison of sodium excretion in response to infusion of isotonic saline into the vena porta and vena cava of conscious rats

1. Indwelling non-occlusive catheters were placed in the vena porta and inferior vena cava of female rats several days before experimentation. Isotonic saline or isosmotic glucose (2% of body wt.) was infused into one vein followed one to several days later with an identical infusion into the other vein of each conscious animal. 2. Significantly higher urine flow and sodium excretion resulted from infusion of isotonic saline (0.5 ml/min) into the vena porta than into the vena cava. Modest prehydration or section of the hepatic branch of the right vagus did not affect the differential sodium response. Changes in endogenous creatinine clearance and potassium excretion were not significantly different for the two routes. Mean values for net peak sodium excretion and contemporaneous urine flow, urinary sodium concentration, and fractional sodium excretion were significantly higher for the portal than for the caval infusion while differences in glomerular filtration rate and filtered sodium load were insignificant. No significant difference in sodium excretion resulted from infusion of isosmotic glucose by the two routes. 3. Compared to the response promoted by the isotonic saline load infused at 0.5 ml/min, the differential response in sodium excretion was prolonged when the same load was infused at 0.375 ml/min. Sodium excretion was not significantly different for the two routes when the same isotonic saline load was infused at 0.75 ml/min. 4. These experiments provide evidence for participation of the liver in the control of sodium excretion and suggest release of a hepatic humoral factor which may be controlled by the duration of exposure of the hepatic circulation to an adequate load of isotonic saline.     

Effects on renal water and sodium excretion of infusions of either iso-osmolar saline or a hypo-osmolar solution of non-electrolytes.

The effects of iso-osmolar and hypo-osmolar volume expansion on renal water and sodium excretion were studied in dogs during light chloralose anesthesia. Saline or a hypo-osmolar of glucose and urea was given i.v. (20 ml/kg b.w.t. in 60 min). From the start of this infusion the combined weight of the hydration infusate and the dog was maintained constant by a servo system, which controlled the rate of infusion of a hypo-osmolar solution. Consequently the degree of hydration increased linearly during the infusion period after which it remained constant throughout the experiment. No increase in free water clearance was seen after iso-osmolar volume expansion. The rate of excretion of sodium increased considerably. Hypo-osmolar volume expansion provoked a water diuresis during which the rate of excretion of sodium fell to less than 0.1 mumol/kg b.w.t. min. It is concluded that under the present circumstances infusion of iso-osmolar saline is not associated with a decrease in the rate of secretion of vasopressin.     

Effects of hypotonic, isotonic, and hypertonic fluids on thoracic duct lymph flow

To test whether whole-body lymph flow responses to vascular volume loading depend on osmolality, we measured left thoracic duct lymph flow rate and protein concentration, plasma protein concentration, plasma osmolality, hematocrit, and arterial and venous pressures in pentobarbital-anesthetized, acutely nephrectomized dogs. Hypo- (100 mosmol), iso- (309 mosmol), and hypertonic (600 mosmol) saline, isotonic lactated Ringer solution, and 5% glucose in lactated Ringer solution (580 mosmol) were infused into the jugular vein (20 ml/kg per infusion over 5 min at 30-min intervals). Changes in blood, interstitial, and cellular volumes were calculated from the infused volume and from the hematocrit and plasma osmolality. The hypotonic fluid increased lymph flow about half as much as the isotonic fluid, whereas the hypertonic fluids increased lymph flow about twice as much as the isotonic infusions. Responses appeared independent of the osmotic agent, because hypertonic NaCl was as effective as hypertonic glucose in increasing lymph flow. Responses were not altered appreciably after lowering arterial pressure by 25 mmHg. The major finding of this study is that for every condition we explored, the excess lymph flow over 30 min (ELF in ml X kg-1 X 30 min-1) correlated with the change in interstitial fluid volume (delta ISFV in ml/kg); ELF = 0.076 delta ISFV (r = 0.909). These data suggest that cellular fluid that enters the interstitium is equally effective in increasing thoracic duct lymph flow as is vascular fluid that filters into the interstitium.     

Suppressive action of prolactin on renal response to volume expansion.

The effects of prolactin on rat renal sodium and water handling during volume expansion were studied using clearance techniques. Both control and experimental adult male Wistar rats were prehydrated with an oral water load of volume equal to 2.5% body weight (BW). At least 3 h later, a continuous intravenous infusion of ovine prolactin (NIH-P-S8), 7.1 mug/h per 100 g, was started in the experimental group. After a 1-h steady-state period, the rats were given an intravenous expansion infusion of either hypotonic saline (2.5% BW), isotonic saline (2.5% and 7.5% BW), or blood (2.5% BW). In all control hypotonic and isotonic saline-expanded animals, within 1 h the rats excreted a volume of urine equal to over 50% of the volume of saline infused. The diuretic and natriuretic responses to saline expansion of prolactin-treated rats were significantly smaller than controls. In contrast to the effects of prolactin on the renal response to saline infusions, it did not alter the natriuretic or diuretic response to blood infusion. Prolactin may be counteracting the effects of physical factors on the regulation of sodium reabsorption in the proximal tubule.     

Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.     

Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies.

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0-20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0-08 +/- 0-01 in rats 21-30 days old and 0-14 +/- 0-01 (P less than 0-01) in adults. However, the depression of proximal tubular water re-absorption was equal in both groups (P greater than 0-20). 3. Proximal glomerulotubular balance for water re-absorption was similar in all groups (P less than 0-20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0-17 +/- 0-04) during hypertonic sodium chloride infusion, compared to adults (0-24 +/- 0-01, P less than 0-05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats.     

Hemodynamic mechanisms influencing sodium excretion during angiotensin infusion.

To examine mechanisms of transition between antinatriuresis and natriuresis, angiotensin II was first infused intrarenally (0.001-0.07 mug/kg-min) in anesthetized dogs; glomerular filtration rate (GFR), sodium excretion, and intrarenal pressure (IRP), indicating tubular pressure, fell as during mechanical aortic constriction. During supplementary intravenous infusion (0.10-0.30 mug/kg-min), renal blood flow (RBF) rose toward control (tachyphylaxis). Tubular reabsorption increased but was still 17.1% below control. Filtration fraction averaging 0.31 remained constant. Sodium excretion and IRP exceeded control but were normalized by restoring renal arterial pressure mechanically. During intrarenal angiotensin infusion, carotid constriction increased blood pressure more, but RBF, IRP, and sodium excretion less than intravenous angiotensin. Intrarenal infusion of angiotensin at 0.10-0.20 mug/kg-min increased RBF and sodium excretion more in infused than in contralateral kidneys. Thus, angiotensin natriuresis depends on increased perfusion pressure and is augmented as tachyphylaxis develops. High correlation between sodium excretion and IRP at unchanged filtration fraction suggests a regulation of sodium excretion by hydrostatic rather than oncotic pressures in glomerular and peritubular capillaries.     

Changes in renal hemodynamics and sodium excretion during saline infusion in lambs.

The renal response to a progressive isotonic extracellular volume (ECV) expansion was studied in 13 lambs of two age groups (5-28 days and 48-57 days). Changes in renal hemodynamics induced by the ECV expansion were followed. Intrarenal blood flow was determined by the microsphere method. For determination of the glomerular filtration rate (GFR) standard clearance techniques were used. Recordings were made during control conditions and when normal saline had been infused in amounts up to 4.5% of the body weight. During the infusion there was an increase in sodium excretion both in absolute values and in relationship to GFR. The increase was, however, much less pronounced in the younger lambs. The GFR did not change significantly during saline infusion. The cortical blood flow increased only in the older lambs. As a consequence the quotient between GFR and cortical blood flow decreased in the older lambs. The possibility of a causal relationship between the fall in filtration fraction so obtained and the more pronounced natriuretic response in the older lambs is discussed. The inner to outer cortical blood flow ratio increased more in the younger lambs during saline infusion. The functional significance of an age related blood flow redistribution is, however, not clear.     

Abnormal relationship between sodium excretion and hypertension in spontaneously hypertensive rats

Summary Inulin clearance, single nephron glomerular filtration rate (SNGFR), Na and K excretion were studied following an acute saline infusion in spontaneously hypertensive (Okamoto strain) rats (SH). 1. Hypertonic saline load: experiments were performed in adult and young SH rats. As compared to control normotensive Wistar rats (NT), the sodium excretion rose much less following the load in SH. During the 75 min following the beginning of the load, adult SH excreted 15% (NT: 58%) and young SH 9% (NT=38%) of the sodium load (P<0.01 in both cases). Cin were similar in SH and NT during control period, and a similar increase was observed following the load. The superficial to juxtamedullary SNGFR ratio was 0.80±0.05 in 5 non diuretic adult SH, a value not different from that found in normal rats, and 0.87±0.07 in 3 salt loaded SH, indicating that no significant intrarenal GFR redistribution occurs in SH following an acute hypertonic saline load. 2. Following an isotonic saline load, the results were not different: the percentage of the sodium load excreted was 44±5% and 10±2% in NT and SH adult rats respectively.The possibility that the observed defect in sodium excretion of SH rats involves distal tubular function is suggested by the pattern of evolution in Na and K excretion.This work was partially presented at the Symposium on Current problems of Hypertension, 1973, Mainz (Germany).Maître de Recherches INSERM.     

Quantitative excretion of water and sodium load by isolated dog kidney: Autonomous renal response to blood dilution factors

Summary Totally isolated dog kidneys of the same pairs are perfused with heparinized blood under identical conditions, one of the kidneys being submitted to a supplementary isotonic or hypotonic saline load. Excess sodium is excreted quantitatively as well as excess solute-free water. Autonomous renal response depends on blood dilution, changes in blood pressure being excluded as well as influence of volume expansion or of extrarenal hormonal factors. The experiments demonstrate kidney ability to control quantitatively fast changes in saline balance by autonomous mechanisms in the sense of intrarenal feed-back type relation to blood composition. Dilution factors (plasma sodium, potassium, proteins) control excretion primarily by adjustment of tubular reabsorption to filtration. Moreover, the absence of relation between basal control excretion and response to saline loading in the present experiments suggest that different mechanisms could insure long duration adjustment of the kidney to a definite blood composition and saline balance. It is demonstrated that many effects attributed to volume expansion can be caused by blood dilution; moreover, interference between dilution effects and specific hormonal control by eventual natriuretic factor should be avoided.This work has been performed with the help of the Fonds National de la Recherche Scientifique (Belgium).     

Hypertonic and isotonic saline solutions in dehydration therapy in neonate calves: comparison of clinical profile and serum and urinary concentrations of electrolytes

Sixteen male Holstein calves, from 1 to 9 days old, were used in the study. The purpose was to compare the effect of both hypertonic (NaCl at 7.2%, 2,400 mOsm/l) and isotonic (NaCl at 0.9%, 300 mOsm/l) saline solutions associated with oral rehydrating solution, using the serum biochemical profile, serum and urinary osmolality, and electrolytic renal clearance and excretion in neonate calves with osmotic diarrhea-induced dehydration. Calves were randomly distributed into four groups: group 1, normal; group 2, treatment with hypertonic saline plus oral solution; group 3, treatment with isotonic saline plus oral solution; and group 4, with no treatment (diarrhea control group). Animals with no treatment presented aqueous diarrhea, severe hyponatremia, hypochloremia, hypokalemia, decrease of rhythm of glomerular filtration, hyperphosphatemia, and azotemia. The use of small volumes of hypertonic saline solution in a single dose restored the plasma volume, serum sodium and chloride concentrations, and rhythm of glomerular filtration. When compared to isotonic saline, hypertonic saline brought about a less marked hemodilution and reestablished serum potassium concentration and rhythm of glomerular filtration. The use of large volumes of isotonic saline solution is associated with a higher rhythm of glomerular filtration, larger hemodilution, and urinary losses of sodium and chloride. We conclude that a rapid infusion of small volumes of hypertonic saline solution with oral rehydrating solution immediately increases plasma volume, serum osmolality, sodium and chloride seric concentrations, rhythm of glomerular filtration, urinary flow, restoring the volume of extracellular fluid after 24 h constituting a practical and economical alternative to the use of large volumes of isotonic saline solution.

Renal response of the new-born dog to a saline load: the role of intrarenal blood flow distribution

1. The renal response to an intravenous saline load was studied in thirty new-born mongrel dogs aged 1-30 days and in seven adult dogs.2. After the infusion of isotonic saline at a rate of 2.0 ml. min(-1) kg(-1) for 15 min and then at a rate of 0.5 ml. min(-1) kg(-1) for an additional 105 min, the puppies excreted a significantly smaller fraction of the infused sodium than did the adults (P < 0.01).3. Both puppies and adults increased their glomerular filtration rates after the saline load. However, adults excreted a larger fraction of their filtered sodium than did the puppies (P < 0.01).4. There was no correlation between age and the ability to respond to a saline load during the first month of life.5. Intrarenal blood flow distribution was measured by the radioactive microsphere technique. After saline infusion in the puppy there was an increase in outer cortical blood flow but inner cortical blood flow remained relatively constant. The result was a decrease in the ratio of inner to outer cortical blood flow (IC/OC ratio). In contrast the IC/OC ratio tended to increase in the adult dog after saline expansion.6. There was no correlation between the magnitude of change of sodium excretion and the change of intrarenal blood flow distribution in the puppy.7. These results confirm that the natriuretic response of the new-born dog kidney is less efficient than that of the adult dog. This is due primarily to the failure of the puppy kidney to decrease fractional sodium reabsorption. Although the new-born dog alters intrarenal blood flow distribution in response to saline loading this alteration does not appear to play a significant role in sodium excretion.     

Parathormone as a mediator of inorganic phosphate diuresis during saline infusion in the rat

Summary Normal rats were infused with isotonic saline at 0.50 ml/min for 2 hours in order to expand their extracellular fluid volume. Under these conditions fractional excretion of inorganic phosphate was found to be as high as 38.8±3.0% of filtered phosphate, while fractional sodium excretion was 12.9±0.7% of filtered sodium. The combined addition of calcium and magnesium to the infusion solution decreased inorganic phosphate excretion significantly (P<0.001) to 11.2±3.6% (presumably by inhibiting parathyroid gland activity), while sodium excretion was unchanged (13.5±1.1%). Parathyroidectomized rats were infused with isotonic saline at 0.50 ml/min to achieve a similar extent of extracellular fluid volume expansion as in the normal rats. In these animals inorganic phosphate excretion was as low as 0.9±0.9% of filtered phosphate, while sodium excretion was 11.8±2.2% of filtered sodium. Administration of parathormone to volume expanded parathyroidectomized rats resulted in marked increases or inorganic phosphate excretion to 41.5±3.1% of filtered phosphate (P<0.001), while sodium excretion remained unaltered (12.0±2.8% of filtered sodium), thus resembling very closely the results in normal volume expanded rats.From these results it is concluded, that saline induced phosphaturia in normal rats is mediated primarily by parathormone. Furthermore, sodium excretion during volume expansion of extracellular fluid appears to be independent of inorganic phosphate excretion and independent of changes in parathyroid activity.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.     

Sodium balance and the natriuresis of hypertonic saline infusion in dogs.

Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration.     

Natriuresis in conscious dogs caused by increased carotid [Na+] during angiotensin II and aldosterone blockade

The renal response to a selective increase in the Na⁺ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na⁺] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaCl. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na⁺ excretion increased markedly in both series, 103 ± 14 to 678± 84 μmol min^-1 during split-infusion and 90 ± 14 to 496 ± 74 μmol min^-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 ± 0.11 to 2.4 ± 0.8 pg ml^-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 ±11 to 152 ±28 fmol min^-1) than during the isotonic volume expansion (45 ± 14 to 84 ± 16 fmol min^-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na⁺ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.