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Background Due to the known contribution of excess sodium intake on elevations in blood pressure, salt reduction regulations are being introduced in countries all over the world. To study the contribution of sodium intake on cardiovascular disease development, we determined whether left ventricular mass associates with sodium excretion in young adults free from overt cardiovascular disease and those with masked hypertension. Methods We included 681 participants (41% men and 50% black) in a cross-sectional analysis from the African-PREDICT study with complete 24-hour urine collections and successful ambulatory blood pressure monitoring (>70% valid readings). The participants were categorized as normotensive (n = 534) or masked hypertensive (n = 147). In addition, we determined left ventricular mass index (LVMI) along with traditional risk factors. Results Masked hypertensive individuals had higher sodium excretion (149 vs. 128 mmol/L/day) and LVMI (78.1 vs. 69.6 g/m2) than normotensives. In single, partial and multiple regression analyses, LVMI independently associated with higher sodium excretion in the total group of young adults (β = 0.089; p = 0.011). This result was also evident among masked hypertensives (β = 0.215; p = 0.008), but not in normotensives (β = 0.054; p = 0.134). Conclusion Our results indicated that higher sodium excretion (reflecting a higher salt intake) may contribute to increased left ventricular mass, potentially driven by the early development of masked or undetected hypertension.

We hypothesize that delayed natriuresis during mental stress increases the risk of hypertension and other diseases. Our preclinical studies demonstrate an important role for renal endothelin-1 (ET-1) in regulating sodium excretion. Thus, we predict ET-1 may be linked to the delayed stress response in at-risk individuals. We hypothesize that reduced renal ET-1 accounts for derangements in sodium handling under stress, a link never explored in a large human cohort. We determined urinary ET-1 excretion in three observational studies of changes in sodium excretion during mental stress, in which 776 healthy youth (15-19 years) enrolled in a 5-hour protocol (2 hours of rest before and after 1 hour of mental stress). In all studies, 60-minute urine samples were obtained throughout the protocol. Subjects were grouped as retainers (reduced sodium excretion during stress relative to baseline) or excreters (increased sodium excretion during stress relative to baseline). In excreters, ET-1 excretion was significantly increased from baseline to stress (+0.02 pg/min; P .001). In contrast, ET-1 excretion was significantly higher (P = .028) in retainers than excreters at baseline but significantly reduced in retainers under stress (-0.02 pg/min; P .001). ET-1 excretion declined further in retainers during recovery but returned to prestress levels in excreters. Albumin excretion and albumin-to-creatinine ratio were significantly higher in retainers (P = .022, P .001, respectively). Thus, loss of ET-1-dependent natriuresis may account for sodium retention during stress and may predispose retainers to renal diseases such as hypertension and kidney disease.

Aim To evaluate the reliability of the ExSel® autoquestionnaire to detect an excess salt intake (≥ 12 g/24 h) in patients consulting for hypertension and/or renal failure. Method The ExSel® autoquestionnaire (proposed from a population of around 100 hypertensive patients) was filled by 104 consecutive patients. Results were compared to 24 h sodium excretion using the Cohen's kappa test, a Chi2. Sensitivity, specificity, VPP and VPN were calculated. A ROC curve was realized to find an accurate cutoff. Results Mean characteristics of the 101 patients with reliable results were: age of 67 ± 12 years, SBP/DBP 139 ± 23/74 ± 13 mmHg (98% were hypertensives, 47% were not controlled, and 23% had resistant hypertension, 78% had a eGFR Conclusions The ExSel® autoquestionnaire is not adapted to outpatients, mainly hypertensives (98%) followed in a nephrology consultation.

OBJECTIVES: Accurate estimates of sodium (Na) intake are critical for advancing our understanding of Na and cardiovascular disease. The aim of this study was to utilize data from a controlled feeding study to assess the agreement between estimated 24hUNa, calculated from several timed spot urine collections, and known Na intake. METHODS: This secondary analysis used data from the control phase of a potassium intervention study in normotensive men and women (n = 39) to avoid the potential confounding factor of dietary potassium manipulation. Participants followed the controlled diet containing on average 3463 mg Na/d for 3 days. On day 4, participants ate 3 meals in a clinic setting and collected urine every 2 hours starting with a fasting second void. The 24-hour urine collection was completed with the first morning void the following day. Spot urine samples were analyzed for Na and estimated 24hUNa was calculated from all samples using the INTERSALT and Tanaka equations, and from only the fasting second collection using the Kawasaki equation. The relationship between estimated 24hUNa and Na intake was assessed using Spearman correlations, and agreement between estimated 24hUNa and intake was assessed using Wilcoxon Signed Rank Tests and Bland Altman plots. RESULTS: For all timed spot urine samples, estimated 24hUNa using INTERSALT and Kawasaki were significantly correlated with Na intake (all P 0.05). For all timed spot urine samples, estimated 24hUNa using INTERSALT was significantly different from Na intake (all P

Objective To investigate whether 24-hour urinary sodium excretion could be an indicator of the effectiveness of salt supplementation in children with postural orthostatic tachycardia syndrome (POTS). Study design The patient group comprised 30 children with POTS, and the control group comprised 10 healthy children. Serum sodium and 24-hour urinary sodium excretion were measured in all children, and the relationship between 24-hour urinary sodium and symptom severity was analyzed in the 30 patients. At 1 month after initiation of salt supplementation, the receiver operating characteristic curve was used to explore the probability of correctly discriminating responders to salt supplementation from nonresponders using 24-hour urinary sodium excretion as an indicator. Results Patients with POTS had lower 24-hour urinary sodium excretion than controls ( P = .022). Symptom severity was negatively correlated with 24-hour urinary sodium excretion (OR, −0.754; P = .000). The receiver operating characteristic curve demonstrated a sensitivity of 76.9% and specificity of 93% for correct prediction of responders and nonresponders to salt supplementation when a 24-hour urinary sodium excretion of 124 mmol/24 hours was used as the cutoff value. Conclusion Our results indicate that 24-hour sodium excretion of

Hypoxia inducible factor (HIF)-1α-mediated gene activation in the renal medulla in response to high salt intake plays an important role in the control of salt sensitivity of blood pressure. High salt-induced activation of HIF-1α in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1α pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1α levels were induced by either transfection of HIF-1α expression plasmid or chronic infusion of CoCl2 into the renal medulla, which was accompanied by increased expressions of anti-hypertensive genes, cyclooxygenase-2 and heme oxygenase-1. Overexpression of HIF-1α transgenes in the renal medulla enhanced the pressure natriuresis, promoted the sodium excretion and reduced sodium retention after salt overload. As a result, hypertension induced by 2-week high salt was significantly attenuated in rats treated with HIF-1α plasmid or CoCl2. These results suggest that an abnormal HIF-1α in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1α levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.

Objectives Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Background Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Methods Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Results Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. Conclusions The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

Blood pressure is frequently elevated, blood volume is usually normal or increased and plasma renin and aldosterone are usually low in nephrotic syndrome (NS). These observations challenge the conventional view attributing sodium retention in NS to a hypoalbuminemia-induced intravascular volume contraction. Given the pivotal role of nitric oxide (NO) in regulation of renal sodium (Na) handling, vascular resistance and sympathetic activity, we considered that Na retention and hypertension in NS may be associated with impaired NO system. Urinary excretion of Na and NO metabolites (NOx), as well as immunodetectable endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) NO synthases were determined in rats with puromycin aminonucleoside (PAN)-induced NS, rats with protein overload proteinuria, Nagase rats (NAR) with inherited analbuminemia, iNOS inhibitor (aminoguanidine)-treated rats, prenephrotic PAN-treated and placebo-treated control rats. The NS group showed marked proteinuria, hypoalbuminemia, decreased fractional excretion of Na (FENa), reduced urinary NOx excretion, and severe reduction of iNOS and nNOS protein abundance in the kidney. Similar results were found in rats with protein overload proteinuria in which proteinuria was present without hypoalbuminemia. In contrast, despite extreme hypoalbuminemia, NAR showed normal FENa, increased urinary NOx excretion and upregulations of iNOS and nNOS protein abundance in the kidney. Administration of aminoguanidine for 3 weeks lowered FENa in normal rats to levels approximating those found in the NS group. Animals studied 2 days after PAN administration (wherein proteinuria was absent) showed no abnormality. Thus, chronic PAN-induced NS results in downregulation of kidney iNOS and nNOS, which can contribute to the reduction of FENa by augmenting renal tubular Na reabsorption, and preglomerular vasoconstriction. Findings in the NAR, which had profound hypoalbuminemia without proteinuria, and in rats with protein overload proteinuria, which had proteinuria without hypoalbuminemia, point to proteinuria as the primary mediator of kidney iNOS and nNOS deficiency and impaired Na excretion in PAN-induced NS.

This study evaluated the effect of oral crude Vernonia polyanthes Less. hydroalcoholic extract administration (CHE, 0.5 and 1.0 g/kg body wt., daily for 7 days) on arterial blood pressure and renal sodium excretion in conscious rats. CHE administration decreased arterial blood pressure dose-dependently followed by a significant rise in creatinine clearance and a fall in fractional post-proximal sodium excretion was compared to the control group. These results suggest that blood pressure decrease induced by the oral crude Vernonia hydroalcoholic extract may be blunted by reduction of the post-proximal renal sodium excretion. Thus, the present study shows that Vernonia extract is a potential vasodilatation agent in normotensive rats without any effects on renal tubule autoregulation mechanisms.

Many studies showed an association between dietary salt intake, blood pressure and increased CVD risk. The potential reason may be related to vascular structural and functional changes, through alterations in endothelial function. The central retinal arteriolar equivalent and urinary albumin

ACE inhibitors or AT(1) antagonists are powerful therapeutic strategies to slow the progression of renal disease. However, they provide only imperfect protection since they cannot always prevent end-stage renal failure. Innovative approaches are needed to keep patients with chronic kidney disease off dialysis. Blockade of the aldosterone pathway may prove to be such a beneficial therapeutic concept.

Objectives. We sought to determine the relations of left atrial (LA) size to blood pressure, obesity, race, age and left ventricular (LV) mass in hypertension. Background. Although obesity, race and age may influence LV mass, their effects on LA size have not been defined in hypertension. Methods. Left atrial size was measured in 690 men (58% African-Americans) with mild to moderate hypertension (mean [±SD] blood pressure 152 ± 15/98 ± 6 mm Hg) and a high prevalence of LV hypertrophy. Effects of LV mass, adiposity, race, age, physical activity, height, weight, sodium excretion, plasma renin activity and heart rate were examined. Results. Left atrial size was greater (p ≤ 0.0001) in obese (44.2 ± 5.7 mm) than in overweight (41.6 ± 5.9 mm) or normal weight (38.9 ± 6.2 mm) patients. Left atrial enlargement (≥43 mm) was present in 56% of obese patients compared with 42% of overweight and 25% of normal weight hypertensive men. As age increased, white patients had a greater LA size than African-American patients. Although there was no relation between LV mass and LA size in normal weight patients, there was a significant positive relation in obese patients. On multiple regression analysis, obesity was the strongest independent predictor of increased LA size. Conclusions. Obesity is the strongest predictor of LA size in patients with hypertension and amplifies the relation between LA size and LV mass. Race influences effects of age and hypertension on LA size. Because increased LA size and LV mass (also influenced by obesity) are associated with an adverse outcome, these findings underscore the importance of obesity, race and age with regard to the cardiac effects of hypertension. (J Am Coll Cardiol 1997;29:651–8)

The effects of steviol, obtained from Stevia rebaudiana, on renal function were investigated using clearance techniques in Wistar rats. Steviol (0.5, 1.0 and 3.0 mg/kg(-1)/h(-1)iv) elicited no significant changes in mean arterial pressure (MAP), glomerular filtration rate (GFR) and renal effective plasma flow (ERPF). The steviol infusion (1.0 and 3.0 mg/kg(-1)/h(-1)), however, induced a significant increase in the fractional sodium excretion (FeNa(+)), fractional potassium excretion (FeK(+)), and urinary flow as percent of glomerular filtration rate (V/GFR) when compared to controls. The data suggest that the steviol may affect salt and water transport in renal tubules.

SUMMARY Romifidine (80 μg/kg bwt) was injected iv into 6 healthy mares producing a marked increase in urine production over 90 min (from control value of 0.55 ml/kg/min to mean production of 5.39 ml/kg/min). This increase was accompanied by a relative increase in sodium excretion and a small increase in glucose excretion while the excretion and clearance of creatinine remained constant. Except for hyperglycaemia and a small but significant increase in serum phosphorus concentration, romifidine had little effect on serum and plasma constituents. Possible aetiological factors are discussed.

Black and White patients from a VA Medical Center hypertension clinic serving a rural, elderly population were randomly assigned to one of three interventions : a) one session of individualized instruction for 87 mmol/day reduced sodium diet; b) one session of 87 mmol/day reduced sodium diet instruction plus a means of estimating urine electrolyte excretion at home; or c) instructions to maintain the usual diet until reevaluated (control). At 3-month follow-up, reduction in 24-hour urine sodium excretion was significantly greater in participants receiving dietary instructions with feedback than in controls. White participants with access to feedback had the greatest reduction in urine sodium. Results support the feasibility of significant sodium reduction in hypertensive patients following a single intervention session.

The IV infusion of pharmacological doses (0.05 μg · kg −1 · min −1 ) of atrial natriuretic peptide to 16 patients with cirrhosis and ascites induced a significant increase in sodium excretion (65 ± 23 to 517 ± 231 μEq/min), urine volume (10.7 ± 2.3 to 15.7 ± 3.7 mL/min), and glomerular filtration rate (89 ± 4 to 110 ± 4 mL/min) in only 5 patients (responders). No significant changes in these parameters (15 ± 6 to 11 ± 4 μEq/min, 5.5 ± 1.0 to 4.2 ± 1.1 mL/min, and 81 ± 5 to 79 ± 6 mL/min, respectively) were observed in the remaining patients (nonresponders). Compared with responders, nonresponders had significantly lower baseline sodium excretion ( P P P P −1 · h −1 ; P P

On moderate sodium intakes (0.5 mmol/kg/day approx.) sheep are readily divided into those that are predominantly urinary of faecal excretors of sodium (U or F sheep). Water turnover and obligatory sodium loss are lower in F sheep. In view of these differences, sodium preference was examined in U and F sheep offered water and sodium bicarbonate solutions (40 or 300 mmol/l). The F sheep took significantly more of the bicarbonate solutions and, therefore, had sodium intakes that were 51% higher on the lower concentration, 94% higher on the higher concentration. Thus, F sheep not only conserve sodium more readily when it is scarce, they select it more readily when it is available.

In conscious rats pretreatment with indomethacin or flurbiprofen, two chemically unrelated inhibitors of prostaglandin synthesis, reduced urine volume and sodium excretion induced by four diuretics, acetazolamide, amiloride, bendrofluazide and frusemide, or oral sodium chloride loads. The maximum reduction in sodium excretion was limited to approximately 2 mmol/kg Na+ even when sodium excretion was greatly increased. In contrast these inhibitors did not appreciably affect potassium excretion. These results indicate that part of the natriuretic response in the rat to highly and moderately efficacious diuretics and to sodium chloride loading is modified by prostaglandins. We suggest that the lack of effects on potassium excretion indicate that the collecting tubule is the probable site of action.

Role of aldosterone in the control of sodium excretion in patients with advanced chronic renal failure. The factors that regulate sodium and potassium excretion in patients with chronic renal failure have not been fully clarified. The role of aldosterone in the control of sodium and potassium excretion was therefore examined in eight normokalemic patients with chronic renal failure (mean creatinine clearance, 14.3 ml/min). With a normal sodium intake (120 to 151 mEq/24 hr), plasma aldosterone levels were above normal in five of the eight patients and in five of six patients with a creatinine clearance of less than 15 ml/min. Aldosterone levels were further increased in all eight patients by assumption of an upright posture (from a mean of 523 to 1,454 pg/ml, P < 0.01). When seven of the patients were placed on a low sodium diet (10 to 20 mEq/24 hr), mean plasma aldosterone levels increased from 587 to 2,393 pg/ml; (P < 0.02). The low sodium diet was also associated with a fall in mean body of 2.1 kg and a decrease in plasma sodium concentration from 140 to 131 mEq/liter (P < 0.005) in all patients. To further define the physiologic role of the high aldosterone levels, we administered the aldosterone antagonist, spironolactone (300 mg/24 hr), to the patients while they were on a normal sodium diet. The administration of spironolactone was associated with a significant natriuresis, as mean sodium excretion increased from 142 to 173 mEq/24 hr (P < 0.02) and mean body wt decreased by 1.4 kg (P < 0.02). With the administration of spironolactone, the mean potassium excretion decreased from 47 to 41 mEq/24 hr (P < 0.05) as plasma potassium rose from 4.6 to 5.4 mEq/liter (P < 0.01). We conclude that (1) many normokalemic patients with advanced renal failure (creatinine clearance < 15 ml/min) are in a state of hyper-aldosteronism, (2) nevertheless, the secretion of aldosterone in these patients can be stimulated further by posture and volume depletion, and (3) aldosterone plays a physiologic role not only in the maintenance of serum potassium concentration but also as an antinatriuretic force in advanced chronic renal failure.

Cadmium administered to rats decreased urinary sodium excretion. Single doses of 1.0 mg/kg or greater were equally effective. Doses of 0.5 mg/kg or less and 20 multiple doses of 0.5 mg/kg had no effect. A single dose was effective for only a limited time. The greatest decrease in sodium excretion occurred at a time that was 0–12 hr after injection, but an effect was still seen at 24 hr and up to 7 days. The action of hydrochlorothiazide was not altered by either a single 10-mg/kg dose or 20 0.5-mg/kg doses of cadmium. An effect of cadmium on potassium excretion was seen but was less evident than the effect on sodium excretion. The concentration of cadmium in the kidneys was not directly related to its effect on sodium excretion, indicating that the biochemical form and not the amount is the determinative factor. It is postulated that cadmium exerts its effect by an indirect mechanism and not by direct action on the nephron.

Renal blood flow can be a major determinant of solute and water excretion. Several methods have been developed during the last 20 to 30 years to measure renal blood flow in experimental animals and in man [1–4]. The distribution of renal blood flow to the cortex and medulla may also influence sodium excretion [5]. Regional flow rates have therefore also been measured [1, 5–7]. However, doubts have been expressed as to the accuracy of these measurements, partly due to theoretical problems and partly because of disagreement in results between techniques [1, 6]. The recent availability of cine–computed tomography (CT) [8, 9] offers a promising new approach to measuring renal blood flow in man and experimental animals. With short scanning time and a high repetition rate, this technique can record indicator dilution curves in major vessels as well as in different layers of tissue using contrast material as a soluble indicator. CT images give a cross sectional view of the anatomy, eliminating the superimposition problem commonly encountered with other techniques. In addition, selective cannulation of renal vessels can be avoided due to the superb contrast resolution of CT scanners, which allows for opacifying vessels and tissues with only small amounts of contrast medium. The goal of the present study was to explore the capability of high speed CT scanning for measuring regional, renal blood flow in the dog.

Rat renal function was evaluated during acute depletion of glutathione (GSH) produced by different doses of diethyl-maleate (DEM). Significant alterations in renal function were observed when the GSH level diminished. The replenishment of GSH and the restoration of renal function were also investigated at various times after the injection. Similar time courses were observed of both the GSH level and renal functions, but the former was shortest. This suggests that the restoration to normal of GSH renal content was necessary in order to regain appropriate kidney function. Furthermore, the fact that impairment of sodium excretion occurred simultaneously with GSH depletion may be considered as evidence of the first event in GSH protective action. It may be hypothetized that the thick ascending limb is the principal renal target for this deficiency.

Prior inhibition of vasoconstrictors normalizes GFR in postobstructed kidneys. The present studies were designed to analyze the potential contribution of angiotensin II and thromboxane A 2 to the remarkable decrease in glomerular filtration rate (GFR) and renal plasma flow observed after unilateral release of 24-hour bilateral ureteral obstruction. Pretreatment of the animals with inhibitors of either thromboxane or angiotensin synthesis for 48 hours prior to and during obstruction eliminated the contribution of these vasoconstrictors. Inhibition of these vasoconstrictors during the period of obstruction results in a greater increase in renal plasma flow and GFR than when inhibition was accomplished after release of the obstruction. These data suggest a greater role for these vasoconstrictors in the decrease in GFR that occurs with obstruction. Simultaneous inhibition of thromboxane and angiotensin production normalized GFR of the postobstructed kidney. Administration of atrial peptide after release of obstruction in the different groups of rats resulted in further increases in GFR, urine flow and absolute sodium excretion. It is suggested that atrial peptide participates in the renal hemodynamic changes that occur in the postobstructed kidney.

In order to clarify the role of atrial natriuretic polypeptide (ANP) in the brain on regulation of blood pressure and urine output, we examined the effects of intracerebroventricular (i.c.v.) administration of synthetic alpha-human ANP (alpha-hANP) to both anesthetized and conscious rats. In anesthetized rats, i.c.v. injection of angiotension II (A II) caused increases of blood pressure, urine flow and sodium excretion in a dose dependent manner. alpha-HANP alone had no effect on these two parameters. The hypertensive effect of A II was apparently attenuated by concurrent injection of alpha-hANP, while, the diuretic response to A II was not changed by alpha-hANP. In conscious spontaneously hypertensive rats, i.c.v. injection of saralasin (an A II antagonist) produced a decrease in blood pressure. The i.c.v. pretreatment with alpha-hANP significantly potentiated the central depressor effect of saralasin. These findings suggest that brain ANP may be involved in controlling blood pressure in the central renin-angiotensin system.

A continuing medical education quiz on this article (one hour of Category 1 credit) appears on page A125 of this issue. This study assessed renal sodium handling in a group of patients with essential hypertension in whom control of the renal blood supply and aldosterone release by angiotensin II is abnormal ("non-modulating") because of recent evidence that these patients have sodium-sensitive hypertension. Sixty-one patients were studied, 25 as balance was achieved with a daily sodium intake of 10 meq and 36 after a shift from a 10 meq to 200 meq sodium intake for five days. Renal and adrenal responsiveness to angiotensin II was assessed by measurement of para-aminohippurate clearance and plasma aldosterone prior to and during the infusion of 3 ng/kg per minute of angiotensin II, to identify the non-modulator group (n = 32). The half-time of the exponential function relating sodium excretion to time during the three to five days when external balance was being achieved with a 10 meq sodium intake was 23.9 ± 0.3 hours in 60 normal subjects, 24.5 ± 1.8 hours in the patients with essential hypertension in whom renal responsiveness to angiotensin II was normal, and prolonged (p

Miniature swine are sensitive and responsive animals for the study of burn shock resuscitation. In this model the sodium loads requisite for resuscitation of burned swine can exert roughly the same effect although with slower restoration of cardiac output when administered in volumes of 50–75% less than those commonly employed clinically. Sodium excretion is more dependent upon the sodium load than upon the concentration of the saline solution. Plasma had no demonstrable resuscitative effect over and above that provided by its volume and sodium content.

Effect of variations in dietary sodium intake on sodium excretion in mature rats. Sprague-Dawley rats weighing 400g or more were studied to determine whether their continued weight gain affects renal sodium handling. Rats maintained on a wide range of sodium intakes gained 3.9 ± 0.4 g/day. The intercept of a linear regression of intake against urinary excretion provided an estimate of the minimum daily requirement for sodium intake of 247 ±33 µEq/day. When more than this required amount was ingested, the animals excreted the excess quantitatively in the urine. When less was ingested they continued to gain weight at a slower rate, 1.6 ± 0.6 g/day, and remained in positive sodium balance. Nonetheless, they developed a sodium deficit manifested as retention of a sodium challenge. Thus, on an adequate dietary intake the normal physiological state of Sprague-Dawley rats of this size is one of chronic sodium retention rather than neutral sodium balance. In contrast, when inadequate sodium is ingested a deficit develops in the absence of external losses. These observations have important implications for the interpretation of studies of renal sodium handling in these animals.Effet de variations de l'apport sodé alimentaire sur l'excrétion sodique de rats matures. Des rats Sprague-Dawley pesant 400g ou plus ont été étudiés pour déterminer si leur prise de poids continue affecte l'élimination sodée rénale. Des rats maintenus à des apports sodés très variés gagnaient 3,9 ± 0,4 g/jour. L'interception de la régression linéaire de l'apport en fonction de l'excrétion sodée fournissait une estimation de l'apport quotidien minimum nécessaire en sodium, 247 ± 33 µEq/jour. Lorsque plus que cette quantité nécessaire était ingéré, les animaux excrétaient quantitativement cet excès dans les urines. Lorsqu'ils ingéraient moins, ils continuaient à prendre du poids plus lentement, 1,6 ± 0,6 g/jour, et restaient en balance sodée positive. Néanmoins, ils développaient un déficit sodé se manifestant par la rétention d'une surcharge sodée. Ainsi, lors d'un apport alimentaire adéquat, l'état physiologique normal des rats Sprague-Dawley de cette taille est une rétention chronique du sodium, plus qu'une balance sodée neutre. A l'opposé, lorsqu'insuffisamment de sodium est ingéré, un déficit se développe en l'absence de pertes externes. Ces observations ont des implications importantes pour l'interprétation des études de l'élimination rénale du sodium chez ces animaux.

Mechanisms of improvement of water and sodium excretion by immersion in decompensated cirrhotic patients. Eight patients with alcoholic liver disease, ascites, and edema were found to have impaired water (36 ± 6% in 5 hr) and sodium (3.9 ± 1.1 mEq/5 hr) excretion during a 20 ml/kg water load. These patients were submitted to a 5-hr head-out water immersion (HWI) with hemodynamic monitoring (Swan-Ganz). HWI increased cardiac index (3.3 to 4.2 liters/min/m2), right atrial pressure (RAP, 3.9 to 9.0 mm Hg), and wedge capillary pulmonary pressure (9.8 to 15.4 mm Hg) (all P < 0.01). HWI decreased plasma renin activity (6.4 to 4.5 ng/ml/hr, P < 0.001), aldosterone (73 to 43 ng/dl, P < 0.001), arginine vasopressin (AVP, 1.03 ± 0.15 to 0.76 ± 0.08 pg/ml, P < 0.005), norepinephrine (NE, 584 to 435 pg/ml, P < 0.001) and increased the percentage of water load excreted (36 to 63%, P < 0.005) and urinary sodium excretion (3.9 to 9.7 mEq/5 hr, P < 0.05). The percentage of water load excreted was inversely correlated to AVP levels (r = 0.52, P < 0.05) and directly correlated to RAP (r = 0.74, P < 0.05). A significant positive correlation was also found between the increase in fractional excretion of sodium (ΔFENa) and the increase in RAP (r = 0.77, P < 0.001). FENa also correlated inversely with NE levels (r = 0.56, P < 0.05). Thus, central blood volume expansion increases renal water excretion in decompensated cirrhotic patients, at least in part by suppressing AVP, and the magnitude of the increase in water excretion and in FENa correlate most closely with the changes in RAP.Mécanismes de l'amélioration de l'excrétion de l'eau et du sodium par immersion chez des cirrothiques décompensés. Huit malades atteints d'une hépatopathie alcoolique, avec ascite et oedèmes avaient une altération de l'excrétion de l'eau (36 ± 6% en 5 heures) et du sodium (3,9 ± 1,1 mEq/5 heures) pendant une charge hydrique de 20 ml/kg. Ces malades ont été soumis à une immersion dans l'eau tête sortie pendant 5 heures (HWI) avec une surveillance hémodynamique (Swan-Ganz). HWI a augmenté l'index cardiaque (3,3 à 4,2 litres/mn/m2), la pression auriculaire droite (RAP, 3,9 à 9,0 mm Hg), et la pression pariétale capillaire pulmonaire (9,8 ± 15,4 mm Hg) (pour tous P < 0,01). HWI a diminué l'activité rénine plasmatique (6,4 à 4,5 ng/ml/hr, P < 0,001), l'aldostérone (73 à 43 ng/dl, P < 0,001), l'arginine vasopressine (AVP, 1,03 ± 0,15 à 0,76 ± 0,08 pg/ml, P < 0,005), la noradrénaline (NE, 584 à 435 pg/ml, P < 0,001) et a augmenté le pourcentage de la charge hydrique excrétée (de 36 à 63%, P < 0,005) et l'excrétion sodée urinaire (3,9 à 9,7 mEq/5 hr, P < 0,05). Le pourcentage de la charge hydrique excrétée était inversement corrélée au niveau d'AVP (r = 0,52, P < 0,05) et directement corrélée à RAP (r = 0,74, P < 0,05). Une corrélation positive significative a également été trouvée entre l'augmentation de l'excrétion fractionnelle de sodium (ΔFENa) et l'augmentation de RAP (r = 0,77, P < 0,001). FENa était également inversement corrélée avec les niveaux de NE (r = 0,56, P < 0,05). Ainsi l'expansion du volume sanguin central augmente l'excrétion rénale d'eau chez des cirrothiques décompensés, au moins en partie en supprimant l'AVP, et l'amplitude de l'augmentation d'excrétion de l'eau et de FENa est très corrélée avec les modifications de RAP.

Twenty surgical newborn infants aged less than 5 days were selected for study to determine the quantity of sodium administered during operation and the subsequent 48 hours, and to determine their response to this sodium load. There were 6 preterm infants with gestational age 35 weeks or less and 14 full-term infants aged more than 35 weeks. Measurements calculated at 12 hourly intervals for 48 hours after operation included sodium intake, sodium excretion, fractional excretion of sodium, and serum sodium. No special guidelines were utilized for fluid management. The mean sodium intake during the 48-hour study period for the term infants was 15.7 mEq/kg, of which 46% was given during the first 12 hours, and for the premature infants was 17.1 mEq/kg, of which 56% was given during the first 12 hours. In the two groups of patients, the amount of sodium given during the first 12 hours was 470% and 480% of their estimated maintenance requirements, respectively. The mean sodium output during the first 12 hours was low in the term group (1.2 mEq/L) and the premature group (1.3 mEq/L), and subsequently increased reaching maximum levels of 2.3 and 2.1 mEq/L, respectively, by 36 hours. The fractional excretion of sodium exceeded 1.0% in 53% of the term and 94% of the preterm infants. During the study period, the mean serum sodium levels exceeded 145 mEq/L (hypernatremia) in 64% of the term and 67% of the preterm infants. We conclude that the observed hypernatremia was primarily the result of excessive sodium administration during and immediately after operation, compounded by a slightly reduced ability to excrete sodium and a short period of postoperative sodium retention. We recommend reevaluation of the current approach to sodium management to avoid hypernatremia and its potential morbidity.

Summary The changes of the juxtaglomerular index values in the superficial, deep and whole cortical areas of rat kidneys after unilateral papillectomy were analyzed. On the papillectomized side the JGI values showed an increase in the deep, and a decrease in the superficial cortical zone. The changes proved to be significant during the whole experimental period in the juxtamedullary index and between the 4–14 postoperative days in the superficial index values. The tendency of the changes of JGI in the contralateral kidneys was similar to those of the papillectomized kidneys, but significant differences were registered less constantly. These changes are probably the consequences of haemo- dynamic factors. Papillectomy is considered an incompetent model for studying the regulatory function of macula densa in the synthesis of renin.

Homeostatic regulation of fluid and electrolyte balance is essential for survival. The kidney plays a primary role in determining the composition and volume of body fluids. Although numerous factors which regulate this homeostatic balance have been analysed, the humoral control of sodium excretion has been elusive. In this review Philip Needleman and his colleagues deal with the very recent identification of a novel family of peptides - atriopeptins I, II and III - present in the heart that have the capacity to modulate renal and vascular function. They also discuss the future.

Changes in sodium balance and urinary and stool sodium output during orally administered rehydration therapy were studied in 22 well-nourished Turkish infants, aged 2 to 13 months, with acute diarrhea mainly of viral origin. The infants randomly received a rehydration solutin containing either 90 mmol Na/L (ORS 90 ) or 40 mmol Na/L (ORS 40 ). Slight transient hypernatremia was noted in a few infants receiving ORS 90 , and slight transient hyponatremia in a few infants receiving ORS 40 . In both groups, sodium balance increased most rapidly during the first 12 hours of rehydration, and then more slowly because of increased urinary as well as stool sodium output. Sodium balance was always more positive after ORS 90 than after ORS 40 , but the difference did not change much from 12 to 36 hours after therapy was started. Changes in fractional sodium excretion, urinary K/Na quotient, and urinary aldosterone-creatinine quotient were used as indexes of changes in sodium balance. All values were interpreted to indicate that the sodium deficit on admission was corrected within 12 to 18 hours after ORS 90 and, in most cases, after 24 to 36 hours after ORS 40 . Both groups of infants responded well to orally administered rehydration therapy from the clinical viewpoint.

Four male unanesthetized dogs each weighing 22.0-29.0 kg received 0.250 mg/kg iv of bumetanide before (treatment I) and after (treatment II) indomethacin pretreatment. Lactated Ringer's solution was administered intravenously throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Unchanged bumetanide and indomethacin concentrations were analyzed using high-performance liquid chromatography. Sodium was measured by flame photometry and creatinine by colorimetry. Indomethacin pretreatment did not significantly change the pharmacokinetics of bumetanide, affecting neither the total amount of drug nor time course of drug delivered into the urine. In contrast, indomethacin pretreatment resulted in a dramatic reduction in the 4-hr sodium excretion and urine volume. Therefore, a pharmacokinetic interaction may be eliminated as a possible mechanism for the attenuation, by indomethacin, of the natriuretic and diuretic response of bumetanide. Instead, it appears that indomethacin diminishes the response to bumetanide via prostaglandin inhibition.

The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis.