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.

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)

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)

Sodium transport parameters in erythrocytes of patients with primary aldosteronism.

Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+,K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+,K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li+-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p less than 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 +/- 0.29 vs 1.51 +/- 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 +/- 1.5 vs 6.7 +/- 1.9 mM) and the number of the Na+,K+-ATPase sites per RBC (331 +/- 52 vs 385 +/- 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p less than 0.001) increase in the rate constant (1.60 +/- 0.12 x 10(-15) vs 1.28 +/- 0.15 x 10(-15) mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p less than 0.01) after treatment.

Sodium pump parameters of red blood cells in men, women and women taking oral contraceptives.

Three parameters of the sodium pump, the sodium efflux rate, the intracellular sodium content (Nai) and the number of sodium, potassium ATPase sites per red blood cell (sites/rbc) were measured simultaneously on erythrocytes from normal men and women and from women taking oral contraceptives. Significant (p less than 0.002) differences were obtained between normal men and women for sodium efflux (1.68 +/- 0.15 vs 1.52 +/- 0.12 mmoles/L rbc/hr). Among the three measured parameters, there was an inverse relationship (r = -0.74) between Nai and sites/rbc and a linear correlation (r = 0.89) between efflux per site and Nai. A positive correlation (r = 0.78) between the sites/rbc and a first-order rate constant for Na efflux/rbc suggests that one component of the rate constant is the number of sites/rbc. Values for a second-order rate constant, calculated from the assumption that efflux/rbc depends on both Nai and the number of sites/rbc, were similar for normal men and women but significantly (p less than 0.001) higher for women taking oral contraceptives.

Effect of plasma storage on erythrocyte sodium pump measurements.

The possibility that sodium handling in red cells may be an indicator of abnormalities associated with hypertension has encouraged many investigators to study erythrocyte sodium transport. The results have often been in conflict, perhaps because of the variety of laboratory techniques and procedures employed. Investigation into the effect of storage of red cells in plasma showed larger changes when cells were stored at 0 degrees C than at room temperature (19 degrees). At 0 degrees C, sodium efflux via the pump increased 22.1% (p less than 0.001) after 2 hours storage and 54.2% (p less than 0.005) after 4 hrs of storage. At 19 degrees C, sodium efflux values were more scattered after storage, but the mean value was not significantly different even after 4 hours. Intracellular sodium increased 17.3% in cells stored 4 hrs at 0 degrees C; significant changes were not observed when cells were stored 2 hrs at 0 degrees C or 2-4 hours at 19 degrees C. The number of Na, K-ATPase sites per red blood cell did not change with either storage condition. For samples processed within one hour of drawing, or stored at room temperature, there were close correlations between the sodium efflux per site and the intracellular sodium concentration as well as between the intracellular sodium and the sites per red cell. These relationships were not evident for cells stored at 0 degrees C. These data indicate that red cells to be used in pump measurements should be stored at room temperature and should be processed within 2 hours.

An extrarenal source of "renin-like" activity in anephric man.

To examine extrarenal sources of "renin-like" activity plasma was obtained from 19 anephric males. Plasma renin activity (PRA), concentration (PRC) (obtained after addition of exogenous renin substrate) and total renin concentration (TRC) (obtained after acid-activation of plasma and subsequent incubation with exogenous renin substrate) demonstrated values for several anephric patients comparable or above those seen in plasma from 10 normal subjects. Incubation of untreated plasma (PRA and PRC) and acid-dialyzed plasma (TRC) for angiotensin I generation was performed at pH 7.5, at 37 degrees C with EDTA, dimercaprol, and 8-OH-quinoline as angiotensinase and converting enzyme inhibitors. The pH optimum for acid-activation of TRC in anephric plasma was the same as that in normal plasma (pH 3.3). Molecular weight determinations following Sephadex gel chromatography demonstrated that the renin-like enzyme in normal plasma had a molecular weight of about 42,000 before and after acid-activation, while that in anephric plasma had a molecular weight of approximately 61,000. A saliva sample from one anephric subject with the highest levels of PRA, PRC, and TRC in plasma also demonstrated measurable amounts of PRA, PRC, and TRC. The molecular weight of this salivary "renin-like" activity also was 61,000. These observations suggest a possible extrarenal source of "renin-like" activity in anephric man. The physiological significance of these studies remains to be clarified.