Total Exchangeable Sodium Research Articles

Total body water and total exchangeable sodium in patients after ileorectal anastomosis.

Abstract Total body water and total exchangeable sodium were measured in 29 patients who had undergone subtotal colectomy with ileorectal anastomosis for chronic ulcerative colitis more than I year previously and in a control group of 28 normal persons. Significant dehydration and sodium depletion in the patients were not demonstrated when compared with the controls. These findings are in contrast to the dehydration and sodium depletion previously demonstrated in ileostomy patients. Faecal loss of sodium in patients with ileorectal anastomosis was found to be less than in patients with ileostomies. The findings suggest that ileorectal anastomosis carries less risk of long-term, fluid and electrolyte depletion than ileostomy.

The effect of intestinal preparation on fluid and electrolyte balance.

Abstract It has been suggested that circulatory instability in elderly patients after the induction of anaesthesia is frequently accounted for by undiagnosed hypovolaemia, particularly in cases of intestinal cancer when preoperative mechanical bowel preparation has been used. In the present study measurements were made in 25 patients undergoing mechanical bowel preparation for large-bowel cancer surgery. Blood-volume measurements remained within normal limits after bowel preparation, and in 5 patients no change was found in total body exchangeable sodium, extracellular fluid volume, and plasma volume measured before and after bowel preparation. Fluid and electrolyte balance studies in 11 cases showed that renal conservation of sodium occurred in the 24 hours preceding surgery and this is probably accounted for by diminished dietary intake. Circulatory instability after the induction of anaesthesia was commonly encountered but in most cases this was not the result of preoperative dehydration.

Evolving concepts in the quantitative analysis of the determinants of the plasma water sodium concentration and the pathophysiology and treatment of the dysnatremias

The physiologic and clinical implications of the empirical formula originally discovered by Edelman et al [J Clin Invest 37:1236-1256, 1958] relating the plasma water sodium concentration ([Na(+)](pw)) to the total exchangeable sodium (Na(e)), total exchangeable potassium (K(e)), and total body water (TBW) have recently been elucidated. It is quite remarkable that the full significance of the Edelman equation discovered almost 50 years ago had remained unrecognized by clinicians and physiologists until recently. Although Edelman and colleagues had shown that the [Na(+)](pw) is proportional to the magnitude of (Na(e)+ K(e))/TBW, the linear equation relating [Na(+)](pw) to (Na(e)+ K(e))/TBW had a slope greater than unity of 1.11, and a non-zero y intercept of -25.6 whose significance was unrecognized and more often than not ignored. It has recently been demonstrated that the slope and y intercept in this equation are quantitatively determined by several additional physiologic parameters, which in addition to (Na(e)+ K(e))/TBW, play a role both in modulating the [Na(+)](pw) and in the generation of the dysnatremias. Even more remarkably, based only on the theoretical principles of Gibbs-Donnan and osmotic equilibrium, all the physiologic parameters that determine the magnitude of the [Na(+)](pw) can be incorporated into a simple conceptual and mathematical framework that sheds light on a broad of range of seemingly unrelated topics that have heretofore been treated separately clinically, including (1) effect of changes in the mass balance of Na(+), K(+), and H(2)O on the [Na(+)](pw); (2) modulation of [Na(+)](pw) in hyperglycemic states; (3) definition of an isonatric solution; (4) current formulas used to quantitate electrolyte-free water excretion; (5) complex role of K(+) in modulating the [Na(+)](pw); and (6) quantitative analysis of the generation and treatment of the dysnatremias. Moreover, this analysis has also proven to be an indispensable tool for deriving new formulas to aid the clinician in both interpreting the pathogenesis and treating the dysnatremias.

A new formula for predicting alterations in plasma sodium concentration in peritoneal dialysis

Alterations in the plasma water sodium concentration ([Na+]pw) result from changes in the total exchangeable sodium (Na e), total exchangeable potassium (K e), and total body water (TBW). The empirical relationship between the [Na+]pw and Na e, K e, and TBW was originally demonstrated (Edelman IS, Leibman J, O'Meara MP, and Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958), where [Na+]pw = 1.11(Na e + K e)/TBW - 25.6 (Eq. 1). Based on Eq. 1, alterations in the [Na+]pw can be predicted by considering changes in the mass balance of Na+, K+, and H2O. In accounting for the mass balance of Na+, K+, and H2O in patients on peritoneal dialysis, considerations must also be taken to determine the modulating effect of dialysate clearance of Na+ and K+ and fluid changes resulting from this therapeutic modality on the [Na+]pw. In this article, we derive a new formula for predicting alterations in the plasma Na+ concentration ([Na+]p) in patients on peritoneal dialysis, taking into consideration the empirical relationship between the [Na+]pw and Na e, K e, and TBW (Eq. 1) as well as changes in mass balance of Na+ + K+ and H2O.

New insights into the pathophysiology of the dysnatremias: a quantitative analysis.

Recent theoretical considerations have played an important role in advancing our understanding of the physiological mechanisms responsible for perturbing the plasma water sodium concentration ([Na(+)](pw)) in health and disease. Central to these considerations is the original empirical relationship between the [Na(+)](pw) and total exchangeable sodium (Na(e)), total exchangeable potassium (K(e)), and total body water (TBW) initially discovered by Edelman and colleagues (Edelman IS, Leibman J, O'Meara MP, and Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958). The non-zero values of the slope and y-intercept in the Edelman equation are a consequence of the effects of the osmotic coefficient of Na(+) salts at physiological concentrations and Gibbs-Donnan and osmotic equilibrium. Moreover, in addition to Na(e), K(e), and TBW, the physiological components of the y-intercept in this equation play a role in modulating the [Na(+)](pw) and in the generation of the dysnatremias. In this review, the pathophysiological mechanisms underlying the generation and treatment of the dysnatremias are analyzed theoretically and quantitatively. Importantly, the non-zero values of both the slope and y-intercept in the Edelman equation result in several theoretical predictions that can be tested experimentally and have been mathematically incorporated into recently derived equations used to analyze both the generation and the optimal treatment of the dysnatremias. In addition, we review current concepts regarding 1) the role of Gibbs-Donnan and osmotic equilibrium in the determination of the [Na(+)](pw); 2) the modulating effect of osmotically inactive exchangeable Na(+) and K(+) on the [Na(+)](pw); 3) the effect of glucose on the [Na(+)](pw) as reflected by changes in Na(e), K(e), and TBW as well as changes in several components of the y-intercept resulting from the hyperglycemia; and 4) the complex role of K(+) in modulating the [Na(+)](pw).

Are the total exchangeable sodium, total exchangeable potassium and total body water the only determinants of the plasma water sodium concentration?

Are the total exchangeable sodium, total exchangeable potassium and total body water the only determinants of the plasma water sodium concentration?

Effect of saline acclimation on body water and sodium compartmentalization in Pekin ducks (Anas platyrhynchos)

The compartmentalization of body fluids was measured in individual Pekin ducks ( Anas platyrhynchos) drinking freshwater and after sequential acclimation to 300 mM NaCl and 400 mM NaCl. Total body water, extracellular fluid volume, plasma volume and exchangeable sodium pool were measured using (3)H(2)O, [(14)C]-polyethylene glycol, Evans Blue dye, and (22)Na dilution, respectively. Following acclimation to 300 mM NaCl, body mass decreased, but total body water and total exchangeable sodium pool were unaltered. Na and water were redistributed from the extracellular fluid (interstitial fluid) compartment into the intracellular fluid compartment. Following further acclimation to 400 mM NaCl, body mass, total body water and intracellular fluid volume decreased, but exchangeable sodium pool and extracellular fluid volume were unchanged. Our results suggested that, when Pekin ducks drink high but tolerable salinities, they maintain total body water, but redistribute Na(+) and water from interstitial fluid to the intracellular fluid compartment. When stressed beyond their ability to maintain total body water, they lose water from the intracellular fluid.

Increased Red Cell Sodium Lithium Countertransport Activity, Total Exchangeable Sodium, and Hormonal Control of Sodium Balance in Normoalbuminuric Type 1 Diabetes

The relationship between erythrocyte sodium lithium countertransport activity (SLC), total exchangeable sodium (NaE), and hormonal control of renal function was examined in 40 normotensive, normoalbuminuric, non-neuropathic Type 1 diabetic subjects, of whom 8 had elevated SLC (> 0.40 mmol Li h-1l-1 rbc). Eleven health controls with normal SLC, who were of comparable age, body mass, and blood pressure were also studied. By contrast with healthy controls, SLC in Type 1 diabetes was not associated with plasma renin activity (PRA), aldosterone, systolic blood pressure or lean body mass. SLC was also unrelated to atrial natriuretic peptide (ANP) (Type 1 diabetes only) and NaE. NaE was not correlated with any other variables. The relationships between PRA and aldosterone in healthy controls were retained in Type 1 diabetes (R2 0.37 supine, p = 0.00001, and 0.27 ambulant, p = 0.0005), as were respective direct and inverse relations between vasopressin and ANP and both PRA (rs 0.54 to 0.57, rs -0.43 to -0.53), and aldosterone (rs 0.78 to 0.80, rs -0.71 to -0.80). Fasting free serum insulin and vasopressin were both inversely related to ANP (rs -0.91 and -0.71, respectively). In the absence of autonomic dysfunction, hypertension or early nephropathy in Type 1 diabetes, increased SLC or exchangeable sodium were unrelated to each other or with hormonal control of sodium balance, but the homeostatic factors controlling hormonal interaction appear to be maintained. The interaction between insulin and hormonal control of sodium and water balance may be modified by circulating free insulin concentrations.

Hypertension and Diabetes

Elevated blood pressure (BP) is an important risk factor for both the large- and small-vessel complications of diabetes. The following pathogenetic mechanisms have been proposed to explain the association between hypertension and diabetes: increases in total body exchangeable sodium associated with hyperglycemia, alterations in the function of the renin-angiotensin-aldosterone system, and the possible role of insulin resistance. Several prospective studies have shown that both systolic and diastolic BP are important predictors of ischemic heart disease, stroke, and renal disease mortality in diabetic patients. In spite of this strong association, there is little evidence from randomized controlled trials on the efficacy of BP lowering in the prevention of cardiovascular mortality in diabetic patients. Prospective data from the WHO Multinational Study do not provide clear evidence of benefit from treating diastolic BP < 95-100 mm Hg in patients with noninsulin-dependent diabetes.

Sequential in vivo measurements of body composition of calves exposed to natural infection with gastrointestinal nematodes

Sequential in vivo measurements of total body water, exchangeable sodium and exchangeable potassium, made by radioisotopic dilution techniques, were used to determine changes in body composition in calves exposed to natural infections with gastrointestinal nematodes during their first grazing season. Two groups of calves were studied, one of which received a sustained release anthelmintic bolus at turn out. Over the grazing season the bolus-treated calves showed a significantly improved pattern of bodyweight gain, compared with the untreated control calves. There were also significant increases in both total body water and exchangeable potassium, as a percentage of the bodyweight, in the bolus calves compared with the controls. These findings indicated that body protein as a percentage of bodyweight was increased in the bolus animals. The bolus-treated calves also had significantly lower serum pepsinogen concentrations, faecal egg counts and worm burdens.

Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.

The pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved. Hemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2, 60 +/- 2 mm Hg). There was a significant increase in total body water (+21%), extracellular volume (+45%), plasma volume (+45%), blood volume (+88%), and exchangeable sodium (+38.2%). Renal plasma flow was severely reduced (-63.2%), but glomerular filtration rate was only mildly decreased (-32%). Significant increases were seen in plasma norepinephrine (3.5-fold normal), renin activity (7.6-fold normal), vasopressin (twice normal), atrial natriuretic peptide (9.4-fold normal), growth hormone (10.7-fold normal), and cortisol (1.9-fold normal). After recovery, the PaO2 increased (50 +/- 3 mm Hg) and PaCO2 fell (45 +/- 4 mm Hg), and the patients became free from edema. All the body compartments returned toward normal, although they did not entirely reach normal values. Renal plasma flow increased significantly, and glomerular filtration became normal. Right atrial and pulmonary arterial pressures and pulmonary vascular resistance decreased (p less than 0.01). Cardiac output decreased but not significantly. Blood pressure increased but not significantly. However, systemic vascular resistance increased significantly to a normal value. We conclude that patients with edema due to chronic obstructive pulmonary disease have severe retention of salt and water, reduction in renal blood flow and glomerular filtration, and neurohormonal activation similar to that seen in patients with edema due to myocardial disease. However, unlike the latter, in chronic obstructive pulmonary disease cardiac output is normal, and systemic vascular resistance and arterial blood pressure are low. This probably is due to the vasodilator properties of hypercapnia. The consequent low arterial blood pressure may be the stimulus for the neurohormonal activation and retention of salt and water.

Basal and Stimulated Plasma Atrial Natriuretic Factor in Patients With Type 1 Diabetes With and Without Nephropathy

Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl-stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20-199 micrograms min-1) and five had overt nephropathy. Seventeen age- and sex-matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 2 l 0.15 mmol l-1 NaCl was infused over 4 h. Basal erect (0945 h) plasma atrial natriuretic factor was 4.2 +/- 0.5, 3.5 +/- 0.4, 2.5 +/- 0.2, and 2.5 +/- 0.3 pmol l-1 in the control, non-nephropathic, incipient-nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCl infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p less than 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.

Changes in forest soils and vegetation in Søgne, southern Norway, during a 20 year period

An investigation of the edaphic conditions and the vegetation of 21 fixed plots in Søgne municipality, Vest‐Agder, South Norway was carried out in 1967‐69 and 1987. Loss on ignition, pH, total nitrogen, total exchangeable bases, base saturation, exchangeable hydrogen, sodium, potassium, magnesium, calcium and manganese was analysed. The species composition of vascular plants was investigated. The total cover of the bottom layer was scored.The soil pH had decreased in the more basic soils but had increased in the more acidic soils. The organic content had increased and base saturation had decreased in most samples. Na+ had increased in more than half of the plots, Ca2+ and Mg2+ had not changed, and K+ and Mn2+ had decreased in most plots. Salt depositions from the neighbouring North Sea and leaching from the soil accounted for these changes. In many of the parameters opposite changes were found in the poorer soils compared to the richer soils. In the field layer Deschampsia flexuosa, Convallaria majalis had increased, and Oxalis acetocella, Galium odoratum had decreased. The cover of cryptogams had decreased in most of the plots.

Renal, cardiovascular and hormonal characteristics of young adults with autosomal dominant polycystic kidney disease

We studied young adults with autosomal dominant polycystic kidney disease (ADPKD) to determine the characteristics that precede renal impairment. Nineteen affected (A) and 20 unaffected (U) offspring from families with ADPKD showed no significant differences in basal glomerular filtration rate (A: mean 97, SD 19; U: 100, SD 23 ml/min/1.73 m2) or renal functional reserve, but effective renal plasma flow was significantly lower in affected offspring (A: 532, SD 86; U: 605, SD 118 ml/min/1.73 m2, P less than 0.01). Plasma renin activity [A: median 26 (95% CI: 15 to 37); U: 14 (11 to 27) microU/ml, P less than 0.05, one-tailed test] and aldosterone [A: 2.5 (2.0 to 3.0), U: 1.0 (1.5 to 2.0) micrograms/100 ml, P less than 0.04, one-tailed test] were increased in affected offspring despite the higher systolic blood pressure (A: mean 123, SD 5; U: 115, SD 3 mm Hg, P less than 0.02) and significant expansion of total exchangeable sodium (A: 40.8, SD 2.3; U: 38.0, SD 3.5 mmol/kg, P less than 0.01). The ouabain-sensitive component of red cell sodium efflux was less in affected offspring (A: 0.258; SD 0.040; U: 0.288, SD 0.042 hr-1, P less than 0.04) and in both groups was correlated inversely with total exchangeable sodium. Echocardiography revealed no difference in left ventricular mass index nor prevalence of mitral valve prolapse. Potential cyst growth factors such as the glucocorticoids and somatomedin C were similar in both affected and unaffected groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of edema in constrictive pericarditis. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones before and after pericardiectomy.

The pathogenesis of sodium and water accumulation in chronic constrictive pericarditis is not well understood and may differ from that in patients with chronic congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms. Using standard techniques, the hemodynamics, water and electrolyte spaces, renal function, and plasma concentrations of hormones were measured in 16 patients with untreated constrictive pericarditis and were measured again in eight patients after pericardiectomy. The average hemodynamic measurements were as follows: cardiac output, 1.98 l/min/m2; right atrial pressure, 22.9 mm Hg; pulmonary wedge pressure, 24.2 mm Hg; and mean pulmonary artery pressure 30.2 mm Hg. The systemic and pulmonary vascular resistances (36.3 +/- 2.5 and 3.2 +/- 0.3 mm Hg.min.m2/l, respectively) were increased. Significant increases occurred in total body water (36%), extracellular volume (81%), plasma volume (53%), and exchangeable sodium (63%). The renal plasma flow was only moderately decreased (49%), and the glomerular filtration rate was normal. Significant increases also occurred in plasma concentrations of norepinephrine (3.6 times normal), renin activity (7.2 time normal), aldosterone (3.4 times normal), cortisol (1.4 times normal), growth hormone (21.8 times normal), and atrial natriuretic peptide (5 times normal). The ratio of left atrial to aortic diameter measured by echocardiography was only minimally increased (1.29 +/- 0.04), indicating that in constrictive pericarditis the atria are prevented from expanding. The studies repeated after pericardiectomy in the eight patients showed that all measurements returned toward normal. The restricted distensibility of the atria, in constrictive pericarditis, limits the secretion of atrial natriuretic factor and, thus, reduces its natriuretic and diuretic effects. This results in retention of water and sodium greater than that occurring in patients with edema from myocardial disease. The arterial pressure is maintained more by the expansion of the blood volume than by an increase in the peripheral vascular resistance.

Recovery of erythrocyte Na(+)-K(+)-Cl- cotransport activity by enalapril.

We studied total exchangeable sodium, ion transport activity at maximal rate, and erythrocyte Na+ content in response to angiotensin converting enzyme inhibition in mild-to-moderate essential hypertensive patients with normal renal function. Twenty-five patients (mean age 56 years, range 40-62 years) who had abnormal red blood cell Na(+)-K(+)-Cl- cotransport or red blood cell Li(+)-Na+ countertransport were treated with either enalapril (20 mg daily) or hydrochlorothiazide (50 mg daily) during a 30-day period. During the period of enalapril treatment, Na(+)-K+ pump and Na(+)-K(+)-Cl- cotransport increased significantly from 4,282 +/- 255 to 5,236 +/- 325 mumol/l red blood cell/hr (p less than 0.01) and 166 +/- 21 to 220 +/- 24 mumol/l red blood cell/hr (p less than 0.05), respectively. Mean intracellular Na+ content in erythrocytes decreased from 11.4 +/- 0.40 to 10.0 +/- 0.33 mmol/l (p less than 0.01) and exchangeable Na+ from 39.8 +/- 0.6 mmol/kg to 35.6 +/- 0.6 mmol/kg (p less than 0.001). Sodium reduction correlated with the recovery of Na(+)-K(+)-Cl- cotransport activity (r = -0.65, p less than 0.01). During treatment, systolic and diastolic blood pressures were reduced significantly (p less than 0.01). In 12 patients treated with hydrochlorothiazide, Na(+)-K(+)-Cl- cotransport, Na(+)-K+ pump, Na(+)-Li+ countertransport, and Na+ permeability did not change significantly while Na+ content decreased from 11.7 +/- 0.3 to 10.3 +/- 0.2 mmol/l (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased Proximal Tubular Reabsorption of Sodium in Childhood Diabetes Mellitus

Type 1 diabetes mellitus is associated with an increase in total exchangeable body sodium. To delineate a site of possible altered sodium handling, proximal tubular sodium reabsorption (PTRNa) was measured in 30 diabetic children, age 12.0 (range 7-16) yr, duration of diabetes 4.5 (range 0.2-12) yr, and compared with 10 non-diabetic children, age 10.0 (range 8.6-12.5) yr. PTRNa was calculated from the fractional clearance of lithium, which was determined from a single blood sample and a random untimed urine sample, taken between 0700 and 0830 h at home, fasting, before insulin therapy. PTRNa was significantly increased in the diabetic children compared with the non-diabetic children (81.6(SE 1.0) vs 74.2(2.6)%, p = 0.014). There was no relationship of PTRNa with age, duration of diabetes, metabolic control (glycosylated haemoglobin, plasma and urinary glucose, plasma lactate), or urinary protein excretion (albumin, N-acetyl-beta-D-glucosaminidase). Elevated sodium reabsorption in the proximal renal tubule may account for the high total exchangeable body sodium found in Type 1 diabetic patients.

Effects of insulin on renal haemodynamics and sodium handling in normal subjects

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic euglycaemic clamp for 1 h (insulin infusion rate 2 mU kg-1 min-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B: as day A, but without insulin and glucose infusion. During combined volume expansion and hyperinsulinaemia an increase in glomerular filtration rate (GFR) (128 +/- 6 vs 117 +/- 8 ml min-1 1.73 m-2, p less than 0.01) and lithium clearance (CLi) (50 +/- 4 vs 33 +/- 5 ml min-1 1.73 m-2, p less than 0.01) was observed compared with basal conditions. GFR and CLi were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion. Superimposed volume expansion and the concomitant increase in GFR and CLi was accompanied by a subsequent enhanced fractional distal sodium excretion of 27%. The changes in plasma concentrations of aldosterone, renin, angiotensin II, atrial natriuretic peptide and catecholamines did not explain the differences in GFR. An increase in GFR of 10%, comparable with that observed in diabetic patients, was induced by combined hyperinsulinaemia and volume expansion in euglycaemic normal subjects. The enhanced GFR is probably a compensatory response to the sodium retention induced by the action of insulin on the distal tubules.

Enalapril as initial and sole treatment in severe chronic heart failure with sodium retention

Five patients, who had never received any drug treatment but who had severe chronic congestive heart failure with salt and water retention, were studied before and after a single dose of enalapril (10 mg orally). Three patients continued on enalapril as monotherapy (10 mg b.d. orally) for one month. Central haemodynamics, body fluid volumes, renal function and plasma hormones were measured at rest. The initial mean right atrial pressure was 13 ± 4 mm Hg, pulmonary wedge pressure 29 ± 4 mm Hg and cardiac index 1.8 ± 0.2 l/min/m 2. Enalapril, given acutely, caused only small changes. Two patients were withdrawn after the single dose of enalapril and treated with diuretics for clinical reasons. The remaining three patients each lost more than 4 kg in weight after one month of treatment with enalapril alone. Total body exchangeable sodium and total body water were reduced but central haemodynamics were unchanged. Although enalapril was of some benefit when given alone to patients with severe congestive heart failure, all five patients were finally treated with diuretics for clinical reasons. Enalapril is not recommended as the initial and only therapy for patients with severe congestive heart failure.

Studies on the Pathogenesis of Hypertension in Cushing's Disease and Acromegaly

The pathogenesis of the hypertension associated with Cushing's syndrome and with acromegaly is poorly understood. We have investigated the possible roles of sodium retention, activation of the renin-angiotensin system and increased sympathetic nervous system activity in untreated patients. In 11 patients with Cushing's disease, seven of whom were hypertensive, total exchangeable sodium was normal despite increased levels of the mineralocorticoid hormones, 11-deoxy-corticosterone and corticosterone. The renin-angiotensin system was also normal. Cardiac sensitivity to the beta-receptor agonist isoprenaline was increased, but this was not due to an increase in beta-adrenoceptor density. Hypertension in Cushing's disease is neither sodium-dependent nor angiotensin II-mediated, but increased cardiac sensitivity to catecholamines, by increasing cardiac output, may contribute to the pathogenesis of hypertension. In nine patients with acromegaly (three of whom were hypertensive) total exchangeable sodium was elevated. Although no correlation between blood pressure and exchangeable sodium was found, hypertension in acromegaly is probably sodium dependent. No evidence was found for a pathogenetic role for either the renin-angiotensin-aldosterone or the sympathetic nervous system.