Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans

Sodium transport of erythrocytes from normotensive and essential hypertensive subjects was evaluated by determining ouabain-sensitive and ouabain-insensitive sodium efflux rates, Na+-Li+ countertransport rates, Li+-K+ cotransport rate constants (lithium replacing sodium), intracellular sodium concentrations, and the number of Na+,K+-adenosine triphosphatase (ATPase) sites per erythrocyte. Subjects included men and women, blacks and whites. Hypertensive subjects had significantly higher sodium transport than did normotensive subjects for ouabain-sensitive sodium efflux (p less than 0.025) and Na+-Li+ countertransport (p less than 0.001). Sexual differences were noted for ouabain-sensitive (p less than 0.001) and ouabain-insensitive (p less than 0.001) sodium efflux, for intracellular sodium concentration (p less than 0.025), and for the Li+-K+ cotransport rate constant (p less than 0.005), all with higher values for men than for women. Racial differences were noted for ouabain-insensitive sodium efflux (p less than 0.005), Na+-Li+ countertransport (p less than 0.001), and the Li+-K+ cotransport rate constant (p less than 0.001); values were higher in whites than blacks for all three measurements. The number of [3H]ouabain binding sites was lower for blacks (p less than 0.001) and the intracellular sodium concentration was higher for blacks (p less than 0.001). Among all subjects, significant (p less than 0.001) correlations were found between intracellular sodium concentration and the number of Na+,K+-ATPase sites per erythrocyte (r = -0.78) and between the ouabain-sensitive sodium efflux per site and intracellular sodium concentration (r = 0.85, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Na+K+ATPase activity and ouabain binding sites in erythrocytes in hyperthyroidism before and after treatment.

Erythrocyte sodium pump is decreased in hyperthyroid patients. We described the effect of untreated hyperthyroidism on Na+K+ATPase activity, ouabain binding sites and intracellular sodium concentration. We found a reduction in Na+K+ATPase activity and in number of ouabain binding sites with a concomitant increase in intracellular sodium. B-blockade therapy failed to restore normal pump activity and sodium concentration, where only thionamide treatment was successful when it was able to decrease free T3.     

The effect of hyperthyroidism on in vivo aging of erythrocyte ouabain-binding sites and intracellular sodium and potassium

The sodium pump activity of erythrocytes is inhibited in hyperthyroidism, whereas in all other cells it is increased. To examine the possibility that thyroid hormones cause an accelerated loss of membrane proteins during in vivo aging, we determined the number of ouabain-binding sites (OBS) in young and old erythrocytes from 13 hyperthyroid and 13 euthyroid subjects. Erythrocytes were separated according to their cell age by centrifugation. In euthyroid subjects, the median number of OBS decreased from 415 (range, 341-551; mean +/- SEM, 440 +/- 19.1) in young cells to 336 (range, 287-453; mean, 340 +/- 13.6) in old cells. In hyperthyroid subjects the median number of OBS decreased from 290 (range, 190-370; mean, 280 +/- 13.3) in young cells to 207 (range, 155-244; mean, 208 +/- 7.5) in old cells. In hyperthyroid subjects the number of OBS of erythrocytes of all ages was lower than that in euthyroid subjects. The ratio of OBS between young and old cells in hyperthyroid subjects (median, 1.27; mean +/- SD, 1.34 +/- 0.16) was similar to that in euthyroid subjects (median, 1.29; mean, 1.30 +/- 0.12). We conclude that these results do not support the hypothesis that in hyperthyroidism there is accelerated loss of sodium pump sites during the lifespan of erythrocytes in circulation.     

Status of the red cell Na,K-pump in hyper- and hypothyroidism

To investigate the status of the sodium-potassium pump in cells of human subjects with abnormal thyroid function, we measured the number of pump units as well as the cation transport activity of the pump in erythrocytes from 23 hyperthyroid and 7 hypothyroid patients. It was found that the number of Na+-K+-ATPase units in erythrocytes (as measured by ouabain binding) was significantly reduced in hyperthyroidism (mean 36% below controls, p less than 0.001). The rate of rubidium uptake by the same cells was also reduced, but to a smaller extent (mean 9%, p less than 0.02). These changes were reversible with control of the hyperthyroidism. Hypothyroid individuals showed changes in erythrocyte Na+-K+ pump which were in the opposite direction to those seen in hyperthyroidism. It is concluded that thyroid hormone exerts a marked negative influence on the number of Na+-K+ pump units in one easily available human cell type. The direction of the effect suggests a complex relationship between thyroid hormone and the level of the Na,K-ATPase in any one tissue. Whatever the cellular mechanism responsible for the effects observed in the red cell, these changes should provide a measure of thyroid hormone action at a cellular level and this may prove useful in the study of thyroid hormone physiology in man.     

Differences in Erythrocyte Cation (Sodium) Transport Between Chinese and Non Chinese Males

Erythrocyte sodium content, sodium pump activity (ouabain sensitive efflux rate, efflux rate constant, ouabain binding sites and Na⁺, K⁺-ATPase activity), sodium-lithium countertransport and sodium-potassium cotransport activities were measured in 10 European males, 11 non Chinese Asian males and 12 Chinese males. There were no differences between the 3 groups in any of the measurements of active transport. The sodium-lithium countertransport was higher and sodium-potassium cotransport (measured as lithium-potassium cotransport) was lower in Chinese compared to either the Europeans or non Chinese Asians. There were no differences in counter and cotransport activities between the Europeans and non Chinese Asians. Multiple regression analysis showed that the co and countertransport pathways contribute little to the maintenance of erythrocyte sodium content in healthy subjects.     

Alteration in intracellular sodium concentration and ouabain-sensitive ATPase in erythrocytes from hyperthyroid patients.

The activity of the ouabain-sensitive sodium-potassium-activated component of the ATP-hydrolyzing enzyme system (ouabain sensitive ATPase) was studied in the erythrocyte membranes of 10 patients with hyperthyroidism, and found to be decreased in all 10 patients. The mean ouabain-sensitive ATPase activity was 43 +/- 4 nmol Pi/mg tissue/h in the patients, compared with 69 +/- 5 nmol Pi/mg tissue/h in the erythrocyte membranes of 10 paired control subjects. The mean concentration of sodium within the erythrocytes was 10.8 +/- 0.9 nmol/liter of red blood cells in the patients and 7.2 +/- 0.3 nmol/liter of red blood cells in the controls. The decrease in ouabain-sensitive ATPase activity did not appear to be associated with a change in the ligand sensitivity of ATPase, nor was there a difference in the activity of the ouabain-insensitive component of ATPase. Serial studies to follow the effects of treatment of hyperthyroidism on red cell membrane ATPase were performed repeatedly in one of these patients. There was a significant inverse correlation between L-thyroxine (T4) and ouabain-sensitive ATPase, as both variables returned to normal. Normal erythrocyte membranes were assayed for ATPase activity in the presence of varying concentrations of L-triiodothyronine (T3) and T4, and following pre-incubation with T4. No significant effect on erythrocyte membrane ATPase was demonstrated in either series of experiments. It can be concluded from these studies that the decreased sodium efflux in the erythrocytes of patients with hyperthyroidism is associated with a decrease in the activity of the ouabain-sensitive component of ATPase in the erythrocyte membrane. The failure to reproduce this effect in vitro suggests that it does not represent a direct effect of the thyroid hormones on the mature erythrocyte membrane.     

Effect of thyroid status on ouabain binding to the human lymphocyte

Lymphocyte Na-K ATPase was evaluated as an index of thyroid status in man. Lymphocytes from 24 untreated hypothyroid patients and 11 hyperthyroid subjects were sampled in parallel with normal lymphocytes, and Na-K ATPase activity was assessed by measurements of ouabain binding to a plasma membrane fraction or to whole cells. In both systems, ouabain bound saturably and specifically, resulting in linear Scatchard plots. Normal lymphocyte plasma membranes bound 2.30 +/- 0.16 pmol ouabain/mg protein (mean +/- SEM; n = 11), with a Kd of 68 +/- 12 nM. Intact normal lymphocytes bound 3.24 +/- 0.30 pmol ouabain/10(7) cells (n = 14), representing 189,000 sites/cell. In hypothyroidism, ouabain binding, when compared with normal cells sampled on the same day, was reduced by 22.0 +/- 5.3% (n = 11; P less than 0.001) in plasma membranes and by 29.1 +/- 3.5% (n = 14) in whole lymphocytes (P less than 0.001), but there was no significant change in the Kd in the membrane fraction. In 6 subjects, the decrease in ouabain binding to lymphocytes was reversed by thyroid hormone replacement. Red cells from hypothyroid subjects showed normal ouabain binding. Ouabain binding to hyperthyroid plasma membranes (2.42 +/- 0.18 pmol/mg protein) was not significantly different from normal. The results in hypothyroid subjects are consistent with the hypothesis that lymphocyte Na-K ATPase is regulated by thyroid hormones. However, lymphocyte Na-K ATPase does not increase in parallel with elevated thyroid hormone levels in hyperthyroidism. The mechanisms underlying these observations remain to be clarified.     

ERYTHROCYTE OUABAIN BINDING IN PATIENTS RECEIVING THYROXINE

Thyroid hormone action at the cellular level was investigated in euthyroid women who were receiving replacement thyroxine, and whose plasma T4 levels were above the upper reference limit for healthy subjects. There is evidence that erythrocyte sodium pump sites are reduced in number in patients with hyperthyroidism. These sites were measured by the ouabain binding capacity. Plasma T4, free T3 and TSH were also measured, the latter by a high sensitivity fluoroimmunoassay. Three groups of women were investigated; 30 patients receiving T4 with elevated plasma T4 concentrations, 30 age-matched healthy women, and 10 untreated thyrotoxic patients. Erythrocyte ouabain binding was significantly reduced in the thyroxine treated patients, although not to the degree observed in the thyrotoxic patients. Plasma free T3 concentration was increased in 12 of 30 treated patients. TSH was undetectable in 23 of 30 treated patients. The ouabain binding results provide some evidence for increased thyroid hormone action at cellular level in thyroxine treated patients.     

Reduced binding and antilipolytic effect of prostaglandin E2 in adipocytes from patients with hyperthyroidism

The present study was undertaken to evaluate the effect of thyroid hormones on prostaglandin E2 (PGE2) binding and action in human adipocytes. The study consisted of 12 patients with hyperthyroidism and 20 normal subjects. In adipocytes from hyperthyroid patients, there was a 32% decrease in [3H]PGE2-binding sites (P less than 0.01). This reduced binding was accompanied by a 46% reduction in the relative antilipolytic effect of PGE2 in adipocytes from patients with hyperthyroidism. These changes might, then, account for some of the enhanced lipolysis that occurs in hyperthyroid patients. Thyroid hormones significantly increased the lipolytic effect of isoproterenol (P less than 0.01). However, the lipolytic effect of theophylline plus adenosine deaminase and basal lipolysis also were increased in adipocytes from hyperthyroid subjects. The latter findings indicate that thyroid hormones induce a state of increased activation of lipolysis under both basal and stimulated conditions. It is concluded that thyroid hormones reduce the binding and action of PGE2 in human adipocytes, possibly via a cAMP dependent mechanism. These alterations will contribute to accelerated lipid metabolism in the hyperthyroid state.     

ERYTHROCYTE SODIUM-POTASSIUM PUMP IN THYROTOXIC PERIODIC PARALYSIS

To search for a genetic marker in patients with thyrotoxic periodic paralysis (TPP), we studied the erythrocyte sodium-potassium pump activity in 13 patients with TPP; 30 thyrotoxic patients with no history of paralysis (T) and 69 euthyroid controls. In thyrotoxic patients (TPP and T), erythrocyte ouabain sensitive sodium efflux rate constant were decreased while erythrocyte sodium content as increased. All these changes reverted to normal when the patients became euthyroid. Maximal ouabain binding capacity correlated positively with ouabain sensitive sodium efflux rate constant (r = 0.542; p < 0.001; n = 155) and negatively with serum thyroxine concentration (r = -0.571; p < 0.001; n = 60) and erythrocyte sodium content (r = -0.521; p < 0.001; n = 155). In the thyrotoxic state, maximal ouabian binding capacity was just significantly higher in TPP when compared with T (0.268 ± 0.014 and 0.234 ± 0.009 pmol/10⁹ cells respectively; p < 0.05). This difference could not be demonstrated when the patients became euthyroid. Our findings suggest that patients with TPP respond to thyrotoxicosis with a smaller decrement in erythrocyte sodium-potassium ATPase activity than patients without a history of paralysis. However, the difference is too small to represent a useful genetic marker for this disease entity. (Aust NZ J Med 1989; 19: 6–10.)     

Evaluation of sodium and potassium pump activity and number in diabetic erythrocytes

The Na+,K+-ATPase (= Na pump), which produces the concentration gradient of Na+ and K+ across the cell membrane, was studied in diabetic erythrocytes. The activity and number of Na pumps, which are functional and quantitative expression of the Na+,K+-ATPase in erythrocytes, were measured by ouabain-sensitive 42K or 43K influx and by [3H]ouabain binding, respectively. The turnover rate of the pumps was calculated from the two measurements to evaluate in situ activity of the pump. The Na pump activity was found to be higher in the diabetic (193 +/- 12 nmol K+/h . 10(9) cells) than in the normal group (164 +/- 6) (P less than 0.05), though the affinities of the pump for extracellular K+ were not different. The number of Na pumps and the Kd of the pumps for ouabain in the diabetic group were not significantly different from those in the normal group (354 +/- 12 site/cell and 4.33 +/- 0.20 nM). The turnover rate of the diabetic group tended to be higher than that of the normal group. The rate was about one third of the molecular activity reported for Na+,K+-ATPase under optimum conditions. These results indicate that the enzymatic properties as well as the number of Na pumps were not altered in diabetic erythrocytes despite the increased Na pump activity. Therefore the increased activity of the erythrocyte Na pump in diabetes mellitus suggests an increase of cation permeability associated with a possible disorder in the diabetic membrane.     

Therapeutic response to canrenone of patients with essential hypertension as a function of sodium transport anomalies and ouabain sensitivity of erythrocytes

The presence of Na+ transport abnormalities (decreased affinity of the Na+/K+ pump or the Na+, K+ cotransport for internal Na+, increased Na+:Li+ countertransport, increased Na+ leak), Na+ content, Na+/K+ pump activity and sensitivity to ouabain were investigated in erythrocytes from 13 patients with essential hypertension. According to the presence or absence of Na+ transport abnormalities, the patients were divided into two groups: TrNa(+) (n = 9) and TrNa(-) (n = 4) respectively. Compared with TrNa(-) patients, TrNa(+) patients were characterized by: (i) a higher arterial pressure (131.4 +/- 11.8 vs 110.0 +/- 13.2 mmHg, p less than 0.05), (ii) an increased erythrocyte Na+ content (8.9 +/- 1.0 vs 6.3 +/- 0.8 mmol/l.cells, p less than 0.01) associated with (iii) a decreased rate constant of Na+/K+ pump activity (235 +/- 26 vs 309 +/- 45 h-1, p less than 0.05) and (iv) a higher sensitivity to ouabain (0.76 +/- 0.23 vs 1.12 +/- 0.26 microM, p less than 0.05). Oral administration of canrenone 50 mg per day during 7 weeks decreased mean arterial pressure by 10-30 mmHg in 6 out of the 9 TrNa(+) patients. Conversely, it decreased mean arterial pressure in only one out of the 4 TrNa(-) patients. The hypotensive effect of canrenone in TrNa(+) patients was not associated with normalization of their Na+/K+ pump activity. Canrenone did not modify the sensitivity to ouabain of either the TrNa(+) or the TrNa(-) patients. Before treatment, acute injection of ouabain provoked an inhibition of the erythrocyte Na+/K+ pump, without any change in Na+ content.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of chloride on deoxycorticosterone acetate-salt hypertension

Selective sodium loading attenuated the development of hypertension in the deoxycorticosterone acetate (DOCA) treated rat. The DOCA treated rat fed a diet equimolar in sodium to a 7% sodium chloride diet and in chloride to a standard diet, differed in various parameters from the DOCA treated rat fed a 7% sodium chloride diet: it had higher sodium concentration in both erythrocytes and muscles, a higher erythrocyte ouabain sensitive 22Na efflux rate constant (Kos), and a lower norepinephrine turnover rate in the heart and the spleen. These results suggest that the suppressed sympathetic nervous system activity and the activated cell membrane sodium pump contribute in part to the mechanism for the suppression of the development of hypertension in the DOCA-selective sodium loaded rat.     

Erythrocyte thermogenesis in hyperthyroid patients: microcalorimetric investigation of sodium/potassium pump and cell metabolism

Erythrocyte thermogenesis was studied by microcalorimetry in 11 patients before and after treatment for hyperthyroidism. Cell heat production rate and intracellular Na+ and K+ levels were measured in plasma suspensions of erythrocytes with and without specific inhibition of Na/K ATPase by ouabain. The ouabain induced change in the heat production rate (the Na/K pump thermal power); the erythrocyte intracellular Na+ content and the ouabain sensitive Na+ transport were used to estimate the Na/K pump function. The mean value for heat production rate was 131 +/- 4 mW/L erythrocytes before treatment, which is significantly higher than in euthyroid subjects. A significant decrease (P less than 0.01) to normal levels was recorded following therapy. This decrease, as determined in samples with ouabain, correlated to changes in serum levels of triiodothyronine, T3, (r = .74, P less than 0.01). The Na/K pump thermal power was 11 +/- 2 mW/L erythrocytes (8 +/- 2% of total heat production rate) before and 9 +/- 2 mW/L erythrocytes (8 +/- 2%) after treatment. These two values were not different from those obtained in euthyroid subjects. The erythrocyte Na+ content decreased from 9.9 +/- 2.1 to 4.9 +/- 0.5 mmol/L erythrocytes (P less than 0.001) following normalization of thyroid function. The decrease in intracellular Na+ concentration correlated to the decrease in serum T3 levels, but only when calculated from the data obtained in samples with ouabain (r = .60, P less than 0.05). The relative increase in intracellular Na+ concentrations following addition of ouabain was significantly lower (P less than 0.05) before than after treatment for hyperthyroidism, 37 +/- 10% and 61 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased lymphocyte thermogenesis in hyperthyroid patients. Role of Na/K pump function. Evaluation of aerobic/anaerobic metabolism.

The role of the Na/K pump for the increased cell energy expenditure in hyperthyroidism was studied by measuring total lymphocyte heat production rate in samples with and without ouabain inhibition of Na/K ATP-ase. In addition, the relative contribution of aerobic processes to lymphocyte thermogenesis was calculated from oxygen consumption measurements. In 12 patients with clinical and laboratory hyperthyroidism total lymphocyte heat production rate was 3.19 +/- 0.21 pW/cell, significantly higher than in 7 patients with subclinical hyperthyroidism (2.14 +/- 0.11 pW/cell) and in 15 euthyroid subjects (2.26 +/- 0.11 pW/cell) (p less than 0.001). The relative decrease in lymphocyte heat production rate after ouabain, giving a quantitative measure of the activity of the Na/K ATP-ase and reflecting the importance of Na/K pump function for the overall rate of lymphocyte metabolism, was not significantly different between the groups: 19.5 +/- 3.6% in hyperthyroid patients, 14.2 +/- 2.3% in subclinical hyperthyroid patients and 17.8 +/- 3.1% in euthyroid subjects. According to the rate of lymphocyte oxygen consumption, aerobic processes represented 58.4 +/- 6.7% of total lymphocyte energy expenditure in hyperthyroid patients, not significantly different from subclinical hyperthyroidism (62.6 +/- 8.4%) or from euthyroidism (66.6 +/- 2.7%). These data do not support the hypothesis of a specific role of the Na/K pump function for the increased cell thermogenesis in hyperthyroidism and indicate a parallel stimulation of aerobic and anaerobic processes by thyroid hormone excess.     

Linoleic acid supplementation, membrane lipids and leucocyte sodium transport in normotensive humans

Ten normotensive subjects had their omnivore diet supplemented with increasing doses of linoleic acid in the form of safflower seed oil in order to examine the effects of this polyunsaturated fat upon leucocyte sodium transport. Increasing the dose ingested to the limits of tolerance produced a significant decrease in ouabain resistant sodium efflux (P less than 0.05) but no significant change in total or ouabain-sensitive sodium extrusion. Intraleucocytic sodium content was correlated with erythrocyte membrane oleic acid % (r = 0.368, P less than 0.05); leucocyte ouabain resistant flux was correlated with oleic acid % (r = 0.453, P less than 0.01) and linoleic acid % (r = -0.319, P less than 0.05). No such associations were observed with ouabain sensitive sodium extrusion. No changes in body weight or urinary electrolyte excretion were observed. It is concluded that, at physiological concentrations, membrane linoleic acid content influences transmembrane sodium fluxes but not through modulation of sodium pump activity. Furthermore, the beneficial effect of this dietary manoeuvre, observed previously with small increments of safflower seed oil, was not seen in this experiment so the hypotensive activity of this manipulation must be regarded as limited.     

Effect of short term triiodothyronine administration on human leukocyte Rb(K) influx and Na efflux

The effect of short term T3 administration on leukocyte ouabain-sensitive 86Rb(K) influx and Na efflux in normal subjects was investigated. At a dose of 60 micrograms daily for 7 days, T3 induced a significant increase in leukocyte 86Rb(K) influx and a significant fall in plasma K concentrations. Plasma and intracellular Na concentrations did not change. [3H]Ouabain binding, a measure of Na-K ATPase units, did not change. A week after T3 administration, 86Rb(K) influx, Na efflux, and plasma K concentrations were normal. In a series of five hyperthyroid patients, both ouabain-sensitive 86Rb influx and [3H]ouabain binding were significantly greater than in normal subjects. We conclude that T3 stimulates 86Rb(K) influx and Na efflux by leukocytes in vivo independently of [3H]ouabain binding and that this increase is rapidly reversible. However, in hyperthyroid patients both 86Rb influx and [3H]ouabain binding are increased, probably due to prolonged exposure to thyroid hormone excess.     

The characteristics of erythrocyte Na+ transport systems in normal pregnancy and pregnancy-induced hypertension.

OBJECTIVE: To assess the role Na plays in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: We assessed Na and K content, the maximum number of ouabain binding sites, Na(+)-Li+ countertransport and Na(+)-K+ cotransport in erythrocytes from women with untreated PIH, normal pregnant women and healthy non-pregnant women. RESULTS: In normal pregnancy, the Na content of erythrocytes decreased, accompanied by the activation of Na excretion systems. In women with PIH, the Na content of erythrocytes and the Na(+)-K+ cotransport activity significantly increased, whilst erythrocyte K content and the maximum number of ouabain binding sites significantly decreased, compared with observations in normal pregnancy. In both normal pregnancy and PIH, there were no differences in Na(+)-Li+ countertransport. CONCLUSIONS: These results suggest that the increase of erythrocyte Na content in women with PIH may be contributed to by a reduction in the number of ouabain binding sites, whilst Na(+)-K+ cotransport and Na(+)-Li+ countertransport may compensate for this effect in women with PIH.     

Ouabain-binding protein(s) from human plasma

Conservation of the binding site on mammalian Na+,K+-ATPase for cardiac glycosides and the importance of the Na+ pump in mammalian cellular physiology has stimulated the search for a mammalian analog of these plant compounds. One candidate, isolated from brain and blood, appears to be ouabain itself or a closely related isomer, the ouabain-like compound. Little is known about the circulating form. Because human steroid hormones circulate with carrier proteins, we produced a ouabain-specific monoclonal antibody (mAb 1-10) and used it to probe normal human plasma for ouabain-protein carrier complex. Ouabain-like biological activity was isolated in association with protein bands of 80, 50, and 25 kDa. These proteins appear to be human immunoglobulins or immunoglobulin-like because they are recognized by anti-human immunoglobulin antibodies, but not by anti-mouse immunoglobulin antibodies. The protein-containing fractions inhibit the binding of mAb 1-10 to immobilized ouabain, and with further purification on protein A, the immunoglobulin-like protein binds radioactive ouabain with an IC50 of 200 to 600 nmol/L, but binds digoxin with 100-fold less affinity, suggesting specificity for ouabain or its isomer. Active protein fractions after purification on C18 inhibit Na+ pump activity in human erythrocytes (IC50 approximately 4 nmol/L, ouabain equivalents), and this chromatography appears to dissociate the ouabain-like compound from the immunoglobulin protein(s). These immunoglobulin-like molecules may represent a subset of immunoglobulins (< or =0.5% of total protein A immunoglobulin) that function as a reservoir and delivery system for ouabain-like compounds in the modulation of human Na+, K+-ATPase in vivo.     

Effect of diet upon the erythrocyte Na,K pump

The number of erythrocyte Na,K-ATPase pump units has been found to be reduced in some populations of obese humans, but the effect of dietary factors upon the status of the erythrocyte pump has not been delineated. We have measured the number of Na,K-ATPase pump units by [3H]ouabain binding and the activity of the pump by ouabain-inhibitable 86rubidium uptake in response to nutritional maneuvers in several patient groups. There was no consistent change in the number or activity of Na,K-ATPase units in response to 1) an acute 600-cal meal, 2) a 3-day fast or refeeding after a fast in normal weight or obese subjects, 3) 2 weeks of hypocaloric (600 cal) feeding in obese subjects. Individuals with anorexia nervosa were also not significantly different from age- and sex-matched control subjects with respect to the erythrocyte Na,K pump. It is concluded that the circulating erythrocyte does not regulate the number or activity of Na,K pump units in response to short or medium term nutritional maneuvers. Differences between obese and thin populations with respect to the Na,K pump are not likely to be secondary to nutritional differences between the two groups.