Ouabain-sensitive Sodium Efflux Research Articles

Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition

Impaired insulin-mediated vasodilation has been implicated in hypertension that is associated with the metabolic syndrome. The aim of this study was to determine whether an abnormality in membrane fatty acid composition was related to a weakening of insulin's inhibitory effect on agonist-stimulated intracellular free calcium elevation. Mild to moderate hypertensive patients (n = 27) and normotensive controls (n = 11) were studied. Hypertensive patients were divided into normoinsulinemic patients (n = 14) and hyperinsulinemic patients (n = 13) according to the area under the curve of plasma insulin concentrations during a 75-g oral glucose tolerance test. Nonstimulated and arginine-vasopressin (AVP) (1 micromol/l)-stimulated intraplatelet free calcium concentrations (p[Ca(2+)](i)) were measured with or without insulin (100 microU/ml) preincubation. Platelet membrane fatty acid composition, intraerythrocyte sodium content, and the ouabain-sensitive sodium efflux rate constant (K (os)) of erythrocytes were also determined. Insulin preincubation reduced AVP-stimulated p[Ca(2+)](i) elevation in both normotensive controls and hypertensive patients. The inhibitory effect of insulin on AVP-stimulated elevation of p[Ca(2+)](i) (%Inhibition) was significantly (P < 0.05) blunted in hyperinsulinemic hypertensive patients (9.7% +/- 2.4%) as compared to normoinsulinemic hypertensive patients (17.4% +/- 2.7%) and normotensive controls (16.9% +/- 1.7%). In hypertensive patients, the %Inhibition was correlated negatively with saturated fatty acids (SFA) (r = -0.51, P < 0.05) and systolic blood pressure (r = -0.44, P < 0.05), and correlated positively with membrane polyunsaturated fatty acids (PUFA) (r = 0.53, P < 0.01) and K (os) (r = 0.53, P < 0.005). Multiple regression analysis showed that SFA, PUFA, and K (os) were the significant variables for %Inhibition. These findings indicate that an increase in SFA and a decrease in PUFA may cause insulin insensitivity in cellular calcium and sodium handling in hypertension with hyperinsulinemia.

Alteration in ouabain-sensitive sodium potassium pump of erythrocytes during pregnancy induced hypertension: a kinetic study.

The erythrocytes are widely used as model cells for studies of sodium-potassium pump (Na(+)-K(+) pump) in health and disease. Hence, to explore the possible role of the Na(+) transport across the cell membrane in the pathogenesis of pregnancy-induced hypertension (PIH), the present study was conducted to assess the Na(+)-K(+) pump functions in relation to its intrinsic kinetic properties using erythrocytes (RBC). Erythrocyte sodium concentration in pregnancy-induced hypertensive women was significantly (p<0.01) lower in comparison to normotensive pregnant women. On the contrary erythrocyte potassium was significantly higher (p<0.01) in PIH women as compared to normotensive pregnant women. Observed alterations in Na(+) and K(+) concentrations in erythrocytes were associated with significantly (p<001) increased Ouabain-sensitive sodium efflux rate and rate constants in erythrocytes from PIH women. Further, kinetic studies revealed that increased Ouabain-sensitive efflux rate constant in RBC from PIH women was accompanied by increased maximal velocity (V(max)) of Na(+)-K(+) pump. However, the affinity constant (K(m)) was unaltered in both the groups. Therefore, these findings suggest that increased Na(+)-K(+) pump activity in RBC of PIH women could be due to either increased numbers of Na(+)-K(+) pump units of increased numbers of active subunits of Na(+)-K(+) pump possibly due to specific plasma factors in PIH women.

Modulation of ouabain sensitive sodium potassium pump of erythrocytes from patients with chronic renal failure:Role of acute hemodialysis

Significantly higher levels of plasma urea creatinine and potassium were observed in patients with renal failure compared to normal controls. The RBC sodium concentration was raised whereas the RBC potassium concentration was decreased in chronic renal failure. These alterations in the RBC Na+ and K+ concentrations were associated with decrease in ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. However, there was no significant impact of acute hemodialysis on the intracellular electrolytes levels, ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. These findings suggest an intrinsic alteration in the transport capacity of Na(+)-K+ pump which could account for the rise in intracellular sodium and fall in intracellular potassium content in the RBCs of chronic renal failure patients.

Erythrocytic ouabain-sensitive sodium efflux rate constant in pregnancy

To elucidate the physiology of active sodium transport (expressed as erythrocytic ouabain-sensitive sodium efflux rate constant = ERCos) in pregnancy and the influence of dietary sodium intake on that transport, active sodium transport was measured in 52 healthy pregnant women in week 16, 20, 24, 28, 32, 36 or week 38 of gestation. ERCos was not influenced by parity, dietary sodium intake or the development of pregnancy-induced hypertension. A statistical significant shift in ERCos was detected between week 24 and week 28 of gestation accompanied by a shift in intracellular sodium content. The meaning of this change in pregnancy remains unsolved, but an influence of ANP through A-II is suggested.

Basal metabolic rate in adults with growth hormone deficiency and in patients with acromegaly: relationship with lean body mass, plasma insulin level and leucocyte sodium pump activity.

1. The relationship of lean body mass, plasma insulin concentration and leucocyte active sodium transport with basal metabolic rate was investigated in 24 adults with growth hormone deficiency before and after treatment with recombinant human growth hormone and in 10 patients with untreated acromegaly. 2. Based on total-body potassium determined by whole-body 40K counting, patients with acromegaly had increased lean body mass, whereas lack of growth hormone was associated with decreased lean body mass. 3. By indirect calorimetry, patients with acromegaly had increased basal metabolic rates and patients with growth hormone deficiency had decreased values when expressed as percentages of values predicted from the WHO/FAO/UNU equations. Basal metabolic rate expressed in terms of lean body mass was similar in acromegaly and growth hormone deficiency, but was higher than normal in both patient groups. 4. The leucocyte ouabain-sensitive sodium efflux rate constant was decreased in both patients with acromegaly and patients with growth hormone deficiency, and there was no correlation with basal energy expenditure, fasting plasma insulin level or serum growth hormone level. 5. There was no increase in the sodium efflux rate constant in patients with growth hormone deficiency after 1 month on treatment with recombinant human growth hormone. 6. Apparent differences in basal metabolic rate in growth hormone deficiency and acromegaly are due to changes in lean body mass. Both adults with growth hormone deficiency and patients with acromegaly have increased energy expenditure, probably owing to changes in fuel metabolism which are not reflected in the leucocyte sodium pump activity.

Intracellular free magnesium of red blood cells in patients with renal disease.

While serum magnesium (Mg) level is increased in patients with end-stage renal disease (ESRD), it is decreased in renal transplant recipients (TR) receiving ciclosporin. This study was performed to examine the cation metabolism of red blood cells (RBC) in these patients. Intracellular free Mg was measured with 31P-nuclear magnetic resonance spectrometry, and ouabain-sensitive sodium (Na) efflux rate (Eos) was measured from the increase in RBC-Na concentration when RBC were incubated in the presence of ouabain. The ouabain-sensitive Na efflux rate constant (ERCos) was obtained by dividing Eos by RBC-Na concentration. RBC free Mg and ERCos were significantly higher in the TR group than in the ESRD group. There was a significant correlation between RBC free Mg and ERCos (r = 0.474, p less than 0.01). These results support the views that the regulation mechanism for intracellular free Mg is different from that for extracellular Mg in patients with renal disease, and intracellular free Mg modulates Na pump activity of RBC.

Blunted Renal Sodium Excretion During Acute Saline Loading in Normotensive Men With Positive Family Histories of Hypertension

The natriuretic and intra-arterial blood pressure response to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with positive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 +/- 5 years) control group with negative family histories of hypertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hypertension and in controls matched for BMI as compared with lean controls. Sodium excretion increased in all three groups during the saline infusion, while subjects with positive family histories of hypertension disclosed a diminished natriuretic response as compared with the two control groups. Systolic blood pressure increased significantly during the saline load in subjects with positive family histories of hypertension, while in subjects with negative family histories of hypertension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium excretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive family histories of hypertension exhibit a blunted natriuretic and an exaggerated blood pressure response to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin.

Erythrocyte sodium fluxes, ouabain binding sites, and Na +, K +-ATPase activity in hyperthyroidism

Erythrocyte sodium pump activity, in contrast to other tissues, is decreased in hyperthyroidism. In order to examine whether the effect of thyroid hormones on erythrocytes is part of a generalized effect on other transport pathways, we measured sodium pump activity, Na +,K +-adenosine triphosphatase (ATPase) activity, ouabain binding sites, bumetanide-sensitive sodium potassium cotransport (SPC), sodium lithium countertransport (SLC), and ouabain- and bumetanide-insensitive passive efflux of sodium (sodium “leak”) in erythrocytes from 20 healthy subjects and 18 untreated hyperthyroid subjects. Sodium pump activity (ouabain-sensitive sodium efflux rate constant), Na +,K +-ATPase activity, and the number of ouabain binding sites were lower and the erythrocyte sodium content was higher in hyperthyroid subjects. The rate constants of erythrocyte SPC ( P < .05), SLC ( P < .001), and sodium “leak” ( P < .05) were also significantly lower in hyperthyroidism. In 11 of the hyperthyroid subjects, sodium flux measurements were repeated after 20 weeks of treatment. Sodium pump activity, the number of ouabain binding sites, and the rate constant for SLC increased. These results suggest that the effect of thyroid hormones on the erythrocyte sodium pump is part of a generalized effect on membrane proteins, rather than a specific effect.

Sodium Content and Sodium Efflux of Mononuclear Leucocytes From Young Subjects at Increased Risk of Developing Essential Hypertension

Mononuclear leucocytes were used as a cellular model for the in vitro measurements of volume, sodium and potassium content, sodium efflux rate constants and absolute sodium efflux in order to assess any cellular changes in young men at increased risk of developing essential hypertension, and to analyze whether any such changes were associated with borderline hypertension and/or heredity. Four groups of subjects were evaluated: 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives, 12 borderline hypertensives with normotensive parents (BH) and 28 normotensive subjects with normotensive parents (NT). The cellular sodium/potassium contents of the four groups were not discernibly different. Ouabain insensitive sodium efflux rate constant and corresponding absolute efflux were significantly increased in offspring of hypertensives. Ouabain sensitive absolute sodium efflux was significantly increased in borderline hypertensives (BHO + BH) compared to normotensives (NT + NTO). These results indicate that leucocytes from subjects predisposed to hypertension possess an increased ouabain insensitive sodium transport mechanism and in subjects with borderline hypertension the sodium-potassium pump seems activated.

Effect of calcium on blood pressure, platelet aggregation and erythrocyte sodium transport in Dahl salt-sensitive rats

Forty 11-week-old Dahl salt-sensitive rats were divided into four groups matched for blood pressure and weight. Group I was given a sodium-deficient diet, group II a sodium-enriched diet, group III a sodium-enriched diet plus a calcium supplement and group IV a sodium-enriched diet plus nitrendipine, a calcium antagonist. For the first 18 weeks, when the sodium-enriched diet contained 2.6% sodium, there were no differences in blood pressure between the groups; the sodium content was then increased to 8%, and the diets continued for 12 more weeks. At 41 weeks old, the rats in group II had significantly (P less than 0.05) higher systolic blood pressures than the other groups. Erythrocytes from the rats on the low-sodium diet had significantly (P less than 0.025) lower intracellular sodium (3.9 +/- 0.4 mmol/l) while cells from the rats given nitrendipine had significantly (P less than 0.005) higher intracellular sodium (13.3 +/- 0.8 mmol/l) than those from the rats on a high-salt diet (7.4 +/- 1.4 mmol/l). Nitrendipine caused significant (P less than 0.05) decreases in both ouabain-sensitive and furosemide-sensitive sodium efflux. Platelet aggregation in response to 2 mumol/l adenosine diphosphate was not significantly affected by the nitrendipine. The evidence that nitrendipine markedly affects sodium transport supports the hypothesis that an interaction of calcium and sodium may be involved in blood pressure control.

Effect of Age, Weight, Race and Sex on Blood Pressure and Erythrocyte Sodium Pump Characteristics

In order to examine whether erythrocyte membrane handling of sodium is influenced by factors other than hypertension, measurements of red cell sodium transport were studied in one hundred normotensive volunteers. Erythrocyte sodium content was found to increase with increasing age, body weight and mean arterial pressure (MAP). It is also significantly correlated with age, body weight and MAP. Total sodium efflux was found to be reduced and negatively correlated with age and body weight. A reduction in ouabain-sensitive sodium efflux was also observed with increasing age and body weight. In males, the rate of ouabain-sensitive sodium efflux is higher than in females. Race was found to have no effect on erythrocyte electrolyte content and cationic flux rates of subjects. These data suggest that when studies in hypertension are going to be carried out, control subjects carefully matched for age, body weight and sex should be used if confounding results are not to be obtained.

Erythrocyte sodium transport and blood pressure in white subjects.

The mechanisms that define the relation between blood pressure and sodium handling are not yet well understood. Although several abnormalities in sodium transport have been associated with hypertension, a link between the blood pressure of normotensive subjects and the erythrocyte sodium-potassium adenosine triphosphatase pump, the principal sodium transporter of sodium, has not been previously demonstrated. Data from independent measurements of erythrocyte intracellular sodium, ouabain-sensitive sodium efflux, and the number of sodium pump sites per red blood cell were used to calculate a second-order rate constant for ouabain-sensitive sodium efflux. Among 20 normotensive white subjects, this rate constant correlated significantly (p less than 0.005) with mean arterial blood pressure. A significant correlation was not observed between the rate constant and the blood pressure of 22 hypertensive subjects. A hypothesis is proposed, which suggests that the sodium efflux rate constant of erythrocytes is related to the control of sodium reabsorption via the sodium pump of the renal tubules and that an elevated erythrocyte rate constant may be associated with chronic increased sodium reabsorption, which leads to volume expansion and the development of hypertension.

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 binding and ouabain sensitive sodium efflux rate constant were decreased while erythrocyte sodium content was 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 less than 0.001; n = 155) and negatively with serum thyroxine concentration (r = -0.571; p less than 0.001; n = 60) and erythrocyte sodium content (r = -0.521; p less than 0.001; n = 155). In the thyrotoxic state, maximal ouabain binding capacity was just significantly higher in TPP when compared with T (0.268 +/- 0.014 and 0.234 +/- 0.009 pmol/10(9) cells respectively; p less than 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

Sodium chloride sensitivity, intracellular sodium concentration in erythrocytes and lymphocytes, and renin profile in essential hypertension.

In order to clarify the possible relationship between changes in blood pressure after salt loading, membrane sodium transport and renin profile, 19 patients with essential hypertension (8 patients with low renin hypertension and 11 patients with normal renin hypertension), admitted to our hospital, were studied. We also examined the correlation of changes in intracellular sodium concentration after salt loading between erythrocytes and lymphocytes. After a control period of one week, all subjects were placed on a low salt intake for one week followed by one week of a high salt intake. Percent increases in mean blood pressure and intracellular sodium concentration in erythrocytes and in lymphocytes after salt loading were greater in low renin hypertensive patients than in normal renin hypertensives. Percent changes in intracellular sodium concentration in erythrocytes inversely correlated with those in ouabain sensitive sodium efflux rate constant and positively correlated with those in intracellular sodium concentration in lymphocytes. These results suggest that an increase in sodium chloride sensitivity of blood pressure in patients with low renin hypertension may be due to the inhibition of Na+-K+ pump in vascular smooth muscle cell membrane.

Acute sodium loading alters sodium pump in Caucasian hypertensive subjects.

The effect of an acute saline load on the sodium pump was determined from measurements of intracellular sodium and potassium, ouabain-inhibitable sodium efflux, and the number of sodium-potassium adenosine triphosphatase (Na,K-ATPase) sites per cell (using 3H-ouabain binding) of erythrocytes from 22 hypertensive and 21 normotensive subjects before and after a 2-1 infusion of 0.9% saline over a 4-hour period. Before the infusion, ouabain-inhibitable sodium efflux was the only measured parameter that was significantly (p less than 0.025) different between hypertensive (1.65 +/- 0.21 mmol/l red blood cell [RBC]/hr) and normotensive (1.46 +/- 0.25 mmol/l RBC/hr) subjects. After the saline infusion, there was a significant (p less than 0.001) decrease in the ouabain-sensitive sodium efflux of the hypertensive (1.55 +/- 0.22 mmol/l RBC/hr) but not of the normotensive (1.48 +/- 0.43 mmol/l RBC/hr) subjects. Although the changes in intracellular sodium of the normotensive and hypertensive subjects caused by the saline infusion were not significant, the fact that the change was in opposite directions in the two groups yielded a significant (p less than 0.02) differential response. After the saline infusion there was a significant increase in intracellular potassium (p less than 0.001, paired t test) and in the 3H-ouabain-binding affinity constant (p less than 0.001, paired t test) for both hypertensive and normotensive subjects. A second-order rate constant, which is an estimate of the apparent affinity constant of the sodium pump, was calculated from the ouabain-inhibitable sodium efflux, the intracellular sodium, and the number of Na,K-ATPase sites per cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of arterial hypertension in chronic uraemia: the role of reduced Na,K-ATPase activity.

In 38 uraemic dialysed patients (17 normotensive, 21 hypertensive) we measured (1) erythrocyte sodium concentration [Nai] and ouabain-sensitive sodium efflux, and (2) arterial pressure, cardiac index and total peripheral resistance. Erythrocyte Na-K pump activity was lower in hypertensive than in normotensive patients (P less than 0.02). Hypertensive patients had significantly higher peripheral resistance than normotensive patients (P less than 0.05), while the cardiac index was similar in both groups. Inverse correlations were found between the rate constant for ouabain-sensitive sodium efflux in erythrocytes and both systolic and diastolic pressure (r = -0.43 and r = -0.45, respectively; P less than 0.01) and total peripheral resistance (r = -0.76; P less than 0.0001). Our data suggest that reduced sodium transport by the Na-K pump plays a role in the pathogenesis of arterial hypertension in patients with chronic uraemia.

A comparison of endogenous digoxin-like immunoreactivity and sodium transport inhibitory activity in umbilical arterial and venous serum

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured by radioimmunoassay for digoxin in 13 paired samples of arterial and venous umbilical cord serum. EDLI was present in vein and artery, but was higher in the venous samples (P less than 0.025). 2. The venous cord serum inhibited the ouabain-sensitive sodium efflux rate constant of a normal mixed leucocyte population when compared with the effect of arterial cord serum (P less than 0.005). 3. It is suggested that the placenta may be involved in the production or metabolism of neonatal EDLI and of the inhibitor of sodium transport.

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)

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.

Effects of oral magnesium on blood pressure and red cell sodium transport in patients receiving long-term thiazide diuretics for hypertension.

Twenty patients receiving long-term (1.0 to 10.3 years) thiazide diuretic treatment for essential hypertension (Th group) received magnesium supplementation as MgO (600 mg Mg/day) for 4 weeks and placebo for another 4 weeks. Before and at the end of each period, we measured blood pressure; intraerythrocyte magnesium, sodium, and potassium (R-Mg, R-Na, and R-K); and erythrocyte ouabain (10-4 M) sensitive sodium efflux rate constant (Kos). The same measurements were also performed in 21 untreated age-matched essential hypertensives (EHT group). In the Th group, R-Mg was lower, R-Na was higher, and Kos was lower than in the EHT group before magnesium supplementation. Oral magnesium resulted in a significant increase in R-Mg (p less than 0.005) and a decrease in R-Na (p less than 0.01), together with an increase in Kos (p less than 0.005) in the Th group. During magnesium supplementation, the increased Kos was correlated negatively with the lowered R-Na (r = -0.57, p less than 0.01) and positively with the increased R-Mg (r = 0.61, p less than 0.005). Systolic, diastolic, and mean blood pressures were reduced significantly during magnesium administration by a mean of 7.5, 3.0, and 4.5 mm Hg. The results indicate that long-term diuretic treatment may give rise to an intracellular magnesium deficiency and a suppression in cell membrane active transport for sodium, with a resultant increase in intracellular sodium content.(ABSTRACT TRUNCATED AT 250 WORDS)