Abnormal Na+-K+ ATPase kinetics in a subset of essential hypertensive patients

We have performed a kinetic analysis of the interaction of Na+-K+ ATPase with internal Na+ in erythrocytes of 30 normotensive controls and 72 essential hypertensive patients. Neither the maximal rate of ouabain-sensitive sodium efflux (Vmax) nor the internal Na+ content required for half-maximal stimulation (K50%) were significantly different between normotensive and hypertensive patients. Nevertheless, using the 95% confidence limits of the K50% in the normotensive group as a cut-off point, 13 (18.06%) essential hypertensive patients exhibited increased values of this parameter (29.16 +/- 4.31 mmol l-1 cells) revealing decreased affinity of Na+-K+ ATPase for internal Na+ (Pump-hypertensives). The Vmax was also higher in the Pump '-' subset (14.08 +/- 4.85 mmol (1 cells h)-1 vs. 6.92 +/- 1.80; P = 0.0002) and 10 of these 13 hypertensives exhibited a Vmax above the upper end limit of 10.5 mmol (1 cells h)-1, suggesting a compensatory effect. No differences were observed between the Pump '-' subset and the remaining 59 hypertensives without Na+-K+ pump abnormality when basal erythrocyte Na+ content and clinical parameters of hypertension were examined. Decreased apparent affinity of Na+-K+ pump for internal Na+ present in 9-27% of essential hypertensives may be implicated in pathogenetic mechanisms of hypertension.     

Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin-dependent diabetics

It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li+/Na+ exchange, may facilitate cell hypertrophy and hyperplasia. Patients with insulin-dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle. Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin-dependent diabetics (aged 17-68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 micrograms min-1. Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol l-1 cell h-1, the upper normal limit for our laboratory (0.49 +/- 0.10, mean +/- SD). In comparison with the patients with normal countertransport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar. In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r = 0.61, P less than 0.001) and Na+/H+ exchange (r = 0.35, P less than 0.05), independently of the effect of age and blood pressure. Posterior wall thickness was correlated to Li+/Na+ exchange (r = 0.38, P less than 0.05) and h/r to Li+/Na+ exchange (r = 0.41, P less than 0.05) and to Na+/H+ exchange (r = 0.44, P less than 0.05). Li+/Na+ exchange was negatively correlated to cardiac index (r = -0.37, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythrocyte Na+–H+ exchanger kinetics and Na+–Li+ countertransport activity in essential hypertensive patients

The authors measured Na⁺–H⁺ exchanger kinetics together with Na⁺–Li⁺ countertransport V _max in the erythrocytes of 21 subjects with essential hypertension and 16 normotensive control subjects. Na⁺–H⁺ exchanger V _max appeared to be increased in patients with essential hypertension, while the Na⁺–H⁺ exchanger affinity for intracellular proton sites ( K _50%) proved to be unchanged and the index of cooperativity among intracellular proton binding sites as measured by Hill's coefficient (Hill's n ) decreased as compared with normotensive control subjects. Na⁺–Li⁺ countertransport V _max appeared to be higher in patients with essential hypertension than in control subjects. The authors were unable to find any correlations between Na⁺–H⁺ exchanger kinetic parameters and metabolic variables such as parameters of insulin resistance and plasma lipids. On the basis of the data obtained, erythrocyte Na⁺–H⁺ exchanger activity was found to be abnormal in two kinetic variables in essential hypertensive patients and showed no simple linear correlations with the main variables of glucose metabolism, plasma lipids, renin or aldosterone.     

Erythrocyte sodium/lithium countertransport and renal lithium clearance in a random sample of untreated middle-aged men

1. It has been proposed that the enhanced erythrocyte Na+/Li+ countertransport observed in many patients with essential hypertension could be a marker of abnormal renal proximal tubular function. We thus investigated the relationship of blood pressure and Na+/Li+ countertransport to an index of proximal tubular function such as renal Li+ clearance. 2. The study was carried out in a sample of 299 untreated male subjects (aged 21-59 years) randomly selected from a population at work. Na+/Li+ countertransport was measured in a representative sub-group of 176 men. 3. We did not detect statistically significant correlation of either blood pressure or Na+/Li+ countertransport (Vmax) with fractional excretion of Li+, while confirming the existence of a significant continuous association of blood pressure and body mass index with Na+/Li+ countertransport (P less than 0.01). 4. A sub-sample of 57 participants belonging to the lowest or the highest quintiles of Na+/Li+ countertransport distribution repeated the Li+ clearance study after moderate Na+ restriction. 5. Although fractional excretions of Na+ and Li+ were reduced on the low Na+ diet (both P less than 0.001), they did not differ significantly between groups. 6. Our results are at variance with the findings of a recent case-control study in a young age group and suggest that further studies are necessary before a conclusion can be drawn as to the suitability of Na+/Li+ countertransport as a marker of Na+ reabsorption in the renal proximal tubule.     

Effects of an intravenous saline load on erythrocyte sodium transport in normal human subjects

The effects of a 2 litre intravenous infusion of saline (0.9% NaCl solution) over 3 h on erythrocyte transmembrane sodium transport were studied in 12 normal human subjects. After saline infusion a significant (P less than 0.01) reduction of both outward Na+,K+ pump- and Na+,K+ cotransport-mediated Na+ effluxes was observed. The Na+,Li+ countertransport rate and the passive Na+ permeability did not change. The incubation of the subjects' erythrocytes, obtained on a separate occasion, with their own plasma taken after the saline infusion, induced an inhibition of both Na+,K+ pump and Na+,K+ cotransport outward sodium fluxes. The percentage decrease after incubation was closely correlated with the percentage reduction induced by the saline infusion in vivo (r = 0.93 for the pump and r = 0.96 for cotransport; P less than 0.01). These data suggest that extracellular fluid volume expansion affects the release of circulating factors modulating sodium transport by the Na+,K+ pump and by Na+,K+ cotransport.     

Intracellular chloride in essential hypertension

In 25 patients with untreated essential hypertension and 25 healthy controls, erythrocyte intracellular Cl- concentration and activity as well as Na+ activity were measured. Intracellular Cl- concentration in essential hypertensive patients was 70.6 +/- 11.3 as compared with 84.4 +/- 9.5 mmol/l in the controls (P less than 0.001). Intracellular Cl- activity was 77.5 +/- 13.0 mmol/l of cell water in hypertensive patients, the control value being 100.8 +/- 11.0 mmol/l of cell water (P less than 0.001). In the hypertensive group intracellular Na+ activity was 14.3 +/- 4.1 as compared with 7.1 +/- 1.8 mmol/l of cell water in the normotensive group (P less than 0.01). From these results it is suggested that in essential hypertension not only disturbances of cation metabolism, but also of anion metabolism, occur. Possibly the Cl- changes reflect a decreased Cl- inward transport due to an altered Na-K cotransport.     

On the Mechanism of Action of Triamterene: Effects on Transport of Na+, K+, and HVHCO-3 -ions.

The rat salivary duct epithelium, which actively transports Na+, K+, and H+/HCO3- in a manner similar to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene on electrolyte transport. 10(-4) M triamterene completely blocked Na+ resorption and lowered net K+ secretion to half that of controls, whereas HCO3- accumlated in the lumen, probably due to a decrease in H+ secretion. The rates of K+ and H+/HCO3- transport in the presence of triamterene did not differ from those determined after omission of Na+ from the luminal fluid. This was considered to be evidence against a direct action of triamterene on transport of K+ and H+/HCO3-. Triamterene rapidly and reversibly reduced the transepithelial electrical potential difference. This was due to almost complete abolition of Na+ conductance of the luminal membrane at 10(-4) M triamterene, whereas K+ conductance was not altered. Triamterene, administered in vitro from the interstitial side of the isolated duct epithelium was ineffective even at the highest concentrations. The activities of the Na-K-ATPase, the Mg-ATPase and the microsomal HCO3-ATPase were influenced by 10(-4) M triameterene in a similiar fashion. These effects were clearly demonstrated only in the homogenate of the duct tissue and not in intact cells in the isolated duct preparation. Therefore they were considered unspecific. The transport studied demonstrate a primary effect of triamterene on Na+ entry from lumen to cell. Influences on net K+ and H+/HCO3 transport are secondary consequences of functional coupling between movement of Na+ and movement of K+ and H+ across the luminal cell membrane.     

The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading

Abstract. Increased activity of the Na⁺/H⁺ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130–170 mmol d^-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na⁺/H⁺ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d^-1 (n= 8) and 85 vs. 200 mmol d^-1 (n= 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d^-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pH_i) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na⁺-propionate (5–40 mM). Initial pH_i-recovery was taken as the activity of the antiport system and plotted against pH_i-values after acidification. Non-linear regression analysis yielded higher ’apparent’ maximal transport rates in Ht than Nt (Nt: 2·00 pL 0·22; Ht: (3·81 pL 0·59)·10^-3 s^-1; P < 0·025). In contrast, baseline pH_i-values and pH_i-values at half-maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d^-1 for 7 d, ’apparent’ maximal transport rates averaged 2.75 0·20, 2·89 0·17, 2·81 ± 0·18 and (3·62 ± 0·25) · 10^-3 s^-1, respectively. Thus, antiport activity was significantly (P < 0·05) stimulated on the 300 mmol d^-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d^-1) in normotensive volunteers did not affect the erythrocyte Na⁺/K⁺ pump, Na⁺/K⁺ cotransport and Na⁺/Li⁺ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na⁺/H⁺ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension.     

Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy.

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.     

Relevance of erythrocyte Na+/Li+ countertransport measurement in essential hypertension, hyperlipidaemia and diabetic nephropathy: a critical review

In this review the usefulness of the measurement of erythrocyte Na⁺/Li⁺ countertransport (Na⁺/Li⁺ CT) activity is evaluated. In particular, the association between enhanced erythrocyte Na⁺/Li⁺ CT activity and essential hypertension, hyperlipidaemia and diabetic nephropathy is discussed. The conclusion of this review is that elevated erythrocyte Na⁺/Li⁺ CT activity is associated with essential hypertension and hyperlipidaemia. A relationship between Na⁺/Li⁺ CT activity and diabetic nephropathy is less evident. Despite a significant link of Na⁺/Li⁺ CT activity with hypertension and hyperlipidaemia, the diagnostic significance of Na⁺/Li⁺ CT activity is low. This is due to the large overlap between the results of control subjects and patients. The factors that contribute to this broad range are discussed in detail.     

Sodium/lithium countertransport and intracellular calcium concentration in patients with essential hypertension and coronary heart disease

The present study was designed to test the hypothesis that enhanced intracellular calcium signalling and increased sodium/lithium countertransport (Na(+)/Li(+) CT) activity may be associated with coronary heart disease (CHD) in non-diabetic patients with essential hypertension. Platelet-activating factor (PAF)-evoked rises in the intracellular calcium concentration ([Ca(2+)](i)) were measured in Epstein-Barr-virus-immortalized lymphoblasts from 62 hypertensive patients with CHD and 34 patients without CHD. Na(+)/Li(+) CT activity was assessed in erythrocytes from 80 hypertensive patients with CHD and 46 patients without CHD. Baseline values of unstimulated and PAF-stimulated [Ca(2+)](i) were not significantly different between hypertensive subjects with (baseline, 126+/-5 nmol/l; stimulated, 550+/-43 nmol/l) and without (baseline, 125+/-5 nmol/l; stimulated, 654+/-105 nmol/l) CHD. Similarly, Na(+)/Li(+) CT activity was not significantly different between the two groups (patients with CHD, 219+/-8 micromol x l(-1) x h(-1); patients without CHD, 234+/-10 micromol x l(-1) x h(-1)). We conclude that intracellular signal transduction, as indicated by PAF-induced rises in [Ca(2+)](i) and Na(+)/Li(+) CT activity, is not associated with an increased risk of CHD in non-diabetic patients with essential hypertension.     

Measurement by bioluminescence technique of erythrocyte membrane Na+,K+-ATPase activity in hypertensive patients

Erythrocyte membrane Na+,K+-ATPase activity was measured using a bioluminescence technique in 28 hypertensive patients (24 with essential hypertension, 2 with renovascular hypertension and 2 with hypertension secondary to primary hyperaldosteronism) and in 28 normotensive control subjects matched for age and sex. Erythrocyte Na+,K+-ATPase activity was significantly reduced in the patients with essential hypertension (130.9 +/- 11.4 vs. 186.6 +/- 19.5 nmol ATP/mg prot per h; mean values +/- SEM; p less than 0.05) and in the patients with secondary hypertension. A significant negative correlation was found between erythrocyte Na+,K+-ATPase and systolic blood pressure (r = -0.603; p less than 0.01), but not between Na+,K+-ATPase and plasma renin activity or plasma aldosterone levels. These data confirm the findings of a number of previous studies reporting reduced activity of erythrocyte Na+,K+-ATPase possibly related to the presence of a circulatory inhibitor of sodium pump. The method, based on ATP assay by bioluminescence, presents a high degree of specificity as well as simple, rapid execution.     

Aggregation of erythrocyte sodium/lithium countertransport activity in families of patients with immunoglobulin A nephropathy.

1. We evaluated the inheritance of erythrocyte Na+/Li+ countertransport activity in IgA nephropathy by assessing this parameter in 19 patients with biopsy-proven IgA nephropathy and in their 53 relatives (32 parents and 21 siblings). The possible use of erythrocyte Na+/Li+ countertransport activity as a marker of poor prognosis was also evaluated. 2. A significant correlation was found between 'familial' and proband Na+/Li+ countertransport activity, but not between that of spouses. 3. Mean blood pressure, although within the normal range, and Na+/Li+ countertransport activity were significantly higher in patients with proteinuria than in those without proteinuria. 4. Parents of proteinuric patients had a higher Na+/Li+ countertransport activity than parents of non-proteinuric patients. 5. In IgA nephropathy the inheritance of erythrocyte Na+/Li+ countertransport activity was preserved. Therefore genetic factors could play a role in the non-immunological progression of IgA nephropathy.     

Erythrocyte Na+-H+ exchanger and Na+-Li+ countertransport activity in primary aldosteronism

Abstract. Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport V _max in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger V _max appear to be increased in patients with primary aldosteronism and Hill's n , an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport V _max between the two groups studied. We were unable to find any correlations between Na-H exchanger V _max and Na-Li countertransport V _max in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.     

Exogenous factors influencing the human erythrocyte sodium–lithium countertransport system

It has recently been found that the Na+-Li+ countertransport across the human erythrocyte membrane is increased in patients with essential hypertension. We investigated the influence of hypokalaemia, oral contraceptives, diabetes mellitus and essential hypertension on the activity of this transport system. Normal values for the maximal Na+-Li+ transport rate were 0.25 +/- 0.08 mmol l-1 h-1 (males, n = 18) and 0.23 +/- 0.06 (females, n = 14). We found elevated values in women taking oral contraceptives (0.34 +/- 0.07, n = 10, P less than 0.001), in patients with chronic hypokalaemia due to diuretic or laxative abuse (0.41 +/- 0.16, n = 13, P less than 0.005) and in those with essential hypertension (0.32 +/- 0.08, n = 24, P less than 0.001) (all data mean +/- SD). Thus our results with hypertensive patients support the findings of other investigators. However, oral contraceptives and drug-induced hypokalaemia greatly modify this system, indicating a regulation of the Na+-Li+ countertransport by hormones. Thus the transport rate does not seem to be an appropriate test for the diagnosis of essential hypertension.     

Decreased activity of the red blood cell ATPase-dependent Na+ pump in patients with cardiac syndrome X.

Marked Na(+)/Li(+) countertransport hyperactivity and post-load hyperinsulinaemia have been described in 93% of patients with cardiac syndrome X. We hypothesized that more complex abnormalities in Na(+) traffic across the cell membrane are present in these patients. The aim of the present study was to evaluate the activities of the two main transporters responsible for transmembrane Na(+) transport, i.e. the ATPase-dependent Na(+) pump and the Na(+)-K(+)-2Cl(-) co-transporter, in a selected group of patients with cardiac syndrome X. We evaluated 19 patients with cardiac syndrome X and 14 control subjects. The ATPase-dependent Na(+) pump and Na(+)-K(+)-2Cl(-) co-transport activities were assessed from Na(+)-loaded red blood cells by using nystatine, in the presence of furosemide and ouabain, as appropriate. Erythrocyte Na(+)/Li(+) countertransport activity, serum lipid and post-load (75 g of oral glucose) insulin levels were also evaluated. The V(max) of Na(+)/Li(+) countertransport (P=0.0001) and post-load insulin levels (120 min; P=0.001) were confirmed to be higher in patients with syndrome X than in controls. The V(max) of Na(+)-K(+)-2Cl(-) co-transport was similar in patients and controls. By contrast, the V(max) of the ATPase-dependent Na(+) pump was significantly lower (P=0.002) in syndrome X patients (3.13+/-0.87 mmol.h(-1).l(-1)) than in controls (4.28+/-1.10 mmol.h(-1).l(-1)). Serum total cholesterol and triacylglycerol concentrations were also higher in patients with syndrome X than in control subjects (P<0.0001). Thus decreased activity of the ATPase-dependent Na(+) pump was present in patients with cardiac syndrome X. Such an abnormality has the biological potential to augment microvascular tone and the response to constrictor stimuli via increased intracellular free Ca(2+). Of note, syndrome X patients also manifested Na(+)/Li(+) countertransport hyperactivity which, in turn, is known to induce peripheral insulin resistance and consequent abnormalities in insulin secretion and lipid turnover. Thus cardiac syndrome X appears as a multifaceted syndrome presenting with either metabolic or cardiovascular symptoms, or both, based on the expression of complex abnormalities in Na(+) traffic across the cell membrane.     

Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.     

Properties of the Na+-K+ pump in human red cells with increased number of pump sites.

We studied the Na+/K+ pump in red cells from an obese human subject (MAJ) in which the number of pumps/cell was 10-20 times higher than normal. Through measurements of the kinetic properties of several modes of operation of the Na+/K+ pump we determined that the pumps in MAJ cells are kinetically normal. In the presence of adequate metabolic substrate the maximum rates of Na+ pumping and lactate production saturated at 60 and 12 nmol/1 cell per h, respectively. Under physiological conditions pump and "leak" Na+ fluxes were similar in MAJ and normal cells. Since internal Na+ was lower in MAJ than in normal cells (Nai+ approximately 2 and 8 mmol/1 cell, respectively), we conclude that the reduction in cell Na+ allows the Na+/K+ pump in MAJ cells to operate at lower fraction of maximum capacity and to compensate for the increased number of pumps.     

Influence of angiotensin converting enzyme inhibitor (captopril) on kidney epithelial cells in vitro: studies on potassium (86Rb) influx and cellular proliferation

The effects of captopril on potassium influx and cellular proliferation in a dog kidney epithelial cell line (Madin-Darby canine kidney cells, MDCK) were studied. Na+K(+)-ATPase activity and the loop diuretic sensitive Na/K/2Cl- cotransport were measured using 86Rb as tracer substance. Cells were incubated with various concentrations of captopril (1-10 mmol/l). The furosemide sensitive Na/K/2Cl- cotransport was significantly decreased from 1 mmol/l onwards. Na+/K(+)-ATPase activity was lowered only when high amounts (10 mmol/l) of the drug were used. Cell proliferation was measured via [3H]thymidine incorporation. After incubation with 1 mmol/l captopril proliferation was strongly decreased (greater than 50%). Higher amounts (5-10 mmol/l) did not further suppress cell proliferation. The data suggest that natriuresis following ACE inhibition in vivo does not involve a direct effect of captopril on Na+K(+)-ATPase. However, the effect on cell proliferation may be of clinical relevance in respect to a possible mitogenic effect of angiotensin II.     

Abnormalities of sodium transport by sodium, potassium-activated adenosine triphosphatase in erythrocytes from obese children

1. Intracellular Na+ concentration [Na+]i and Na+ extrusion catalysed by sodium potassium-activated adenosine triphosphatase (Na+, K+-pump) were evaluated in erythrocytes from 21 obese children and 20 normal weight- and age-matched controls. 2. Obese children showed a significantly decreased Vmax. for Na+, K+-pump-mediated Na+ efflux (5638 +/- 338 vs 7597 +/- 335 mumol h-1 litre-1 of cells mean +/- SEM, P = 0.01), while [Na+]i (9.3 +/- 0.3 vs 9.1 +/- 0.5 mmol/litre of cells, mean +/- SEM, NS) and Na+ efflux in fresh cells (2380 +/- 153 vs 2533 +/- 180 mumol h-1 litre-1 of cells, mean +/- SEM, NS) were similar in both groups. 3. Mean diastolic blood pressure was significantly higher in obese children than in controls, although both groups were normotensive (73.8 +/- 1.3 vs 66.2 +/- 1.9 mmHg, mean +/- SEM, P = 0.009). 4. Abnormal Na+, K+-pump activity is present in individuals with idiopathic obesity. 5. The possible link between obesity and blood pressure regulation may be mediated through modifications in Na+,K+-pump activity.