Erythrocyte water, Na+-K+ cotransport, and forearm vascular function in humans

We examined the relationships between erythrocyte (RBC) composition (Na+, K+, and water content) and ouabain-insensitive transports (Na+-K+ cotransport, Li+-Na+ countertransport) and forearm vascular hemodynamics under standardized basal conditions and during vasoconstriction (intra-arterial infusion of graded doses of norepinephrine and angiotensin II) and vasodilation (intra-arterial phentolamine and postischemic exercise). RBC water content correlated positively and significantly (r = 0.53, p = 0.001) with minimum forearm vascular resistance, a measure of vascular structural change, and negatively with maximal forearm blood flow (r = -0.55, p less than 0.001). Similar correlations with forearm vascular resistance and blood flow were observed under all experimental conditions. RBC Na+-K+ cotransport correlated positively and significantly (r = 0.43, p = 0.01) with the change in forearm blood flow produced by phentolamine, a functional measure of alpha-adrenergic tone, and was as strong an independent predictor of phentolamine-induced blood flow change as was arterial norepinephrine concentration. RBC Na+-K+ cotransport was also significantly positively correlated with residual forearm blood flow and resistance after phentolamine administration, where nonadrenergic influences predominate. RBC water correlated negatively with Li+-Na+ countertransport (r = -0.33, p less than 0.05) and Na+-K+ cotransport (r = -0.44, p less than 0.01). We propose that RBC water is a marker for a vascular structural property that contributes to vascular reactivity. RBC Na+-K+ cotransport seems to relate most strongly to the sympathetically mediated control of forearm blood flow and may also be linked to the intrinsic myogenic tone of the forearm vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

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)     

Associations of three erythrocyte cation transport systems with plasma lipids in Utah subjects

To investigate the pathophysiology of essential hypertension, detailed biochemical and clinical variables were collected and analyzed for 2091 Utah subjects aged 3 to 83 years. Three different measurements of erythrocyte cation transport were obtained: Na+-Li+ countertransport, Li+-K+ cotransport, and furosemide-insensitive Li+ efflux into MgCl2. Total plasma cholesterol, triglycerides, and high density lipoprotein cholesterol levels were obtained from fasting subjects. Levels of high density lipoprotein subfractions 2 and 3 were also obtained from 350 subjects. Standardized data collection also included blood pressure, height, weight, and presence or absence of a diagnosis or treatment of essential hypertension. In univariate analyses of all 1420 adults, each of the three transport systems showed the same significant correlations with triglyceride levels (r = 0.33-0.35, p less than 0.0001), high density lipoprotein concentration (r = -0.19 to -0.21, p less than 0.001), and weight (r = 0.22-0.28, p less than 0.0001). In multivariate regression analyses, values for each transport system were significantly higher in hypertensive subjects; values for triglycerides, high density lipoprotein, and usually, the high density lipoprotein subfractions continued to have strong significant independent associations with all three transport systems; and weight remained significantly related only to Na+-Li+ countertransport. In separate logistic regressions, plasma triglyceride levels (positively, p less than 0.001) and high density lipoprotein subfraction 3 levels (inversely, p less than 0.03) were associated with hypertension itself. In multivariate analyses among 671 children, high density lipoprotein and high density lipoprotein subfraction 3 levels showed significant (p less than 0.05) inverse correlations with Na+-Li+ countertransport and furosemide-insensitive Li+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure and erythrocyte Na+ transport systems in a French urban male population

This paper reports an investigation of blood pressure (taken as a continuous variable) as a function of: erythrocyte Na+ content; Na+,K+ pump; Na+,K+ cotransport and Na+,Li+ countertransport fluxes, and passive cation permeabilities in fresh erythrocytes from 129 French males who were living in an urban area and were not under treatment for any medical condition (after allowing for the effects of age, body mass index, alcohol and tobacco consumption). In contrast with previous findings in a North American population, we were unable to confirm that blood pressure was correlated with erythrocyte Na+ content and Na+,K+-AT-Pase activity. Conversely, the only transport parameter correlated (negatively) with blood pressure was outward Na+,K+ cotransport [r = -0.20, P less than 0.05 and r = -0.19, P less than 0.05, for systolic (SAP) and diastolic arterial pressure (DAP), respectively; n = 114]. When allowing for age, body mass index and alcohol consumption, the correlation coefficient between the Na+,K+ cotransport system and blood pressure increased from -0.20 to -0.28 (P less than 0.01) for SAP and from -0.19 to -0.28 (P less than 0.01) for DAP (n = 105). We conclude that the correlations between blood pressure and erythrocyte Na+ transport function could differ between North American and French (or Mediterranean) populations. In any case, a decreased pump or outward Na+,K+ cotransport activity may lead hypertensive subjects to a similar increase in cell Na+ (and Ca2+) content in the vascular wall.     

Chronic Alcohol Intake Induces Reversible Disturbances on Cellular Na+ Metabolism in Humans: Its Relationship with Changes in Blood Pressure

The effect of chronic alcohol consumption on Na(+)-K+ ATPase, Na(+)-Li+ countertransport, outward Na(+)-K(+)-Cl- cotransport system and the Na+ leak was investigated in red blood cells from 18 normotensive subjects with a daily alcohol intake of more than 150 g. The study was repeated after 3 months of alcohol withdrawal, and results were compared with a group of 20 healthy normotensive teetotalers. Maximal efflux rate (Vmax) and apparent dissociation constant for internal Na+ (KNa) of the Na(+)-K+ pump and the Na(+)-Li+ countertransport were significantly higher in alcohol consumers. A positive correlation between daily alcohol intake and Vmax of both transport systems (p less than 0.05) was observed. These values significantly decreased after alcohol withdrawal. A simultaneous stimulation of the Na(+)-K(+)-Cl- cotransport system after alcohol withdrawal was also observed. Blood pressure values were higher in alcoholics (133.7/82.3) than in abstainers (121.4/75 mmHg) and significantly decreased (128.5/76.9 mmHg) after withdrawal. A positive correlation between the stimulation of the Na(+)-K(+)-Cl- cotransport and the decrease of blood pressure after withdrawal was observed. In conclusion, chronic alcohol intake induces disturbances on red blood cell Na+ metabolism that dissipate with the cessation of drinking. Similar abnormalities also reported in humans and animals with primary hypertension have been associated in the pathogenesis of essential hypertension. Therefore, the pressor effect of chronic alcohol intake could be mediated through these changes in cellular Na+ metabolism.     

Mixture analysis of erythrocyte lithium-sodium countertransport and blood pressure

This study employs multivariate normal mixture analysis, a technique for identifying discrete subgroups within populations, to examine the relation of erythrocyte lithium-sodium (RBC Li+-Na+) countertransport and blood pressure in a group of 474 healthy adults. After adjusting for effects of age, gender, race, height, and weight, univariate mixture analysis of the distribution of mean arterial blood pressure (MAP) revealed the presence of only one group, whereas the distribution of RBC Li+-Na+ countertransport values was composed of a mixture of two groups (p less than 0.00005). When bivariate mixture analysis was applied to the combined distribution of MAP and RBC Li+-Na+ countertransport, two commingled subgroups were identified (p less than 0.00005). The smaller group (19%) had significantly higher values for both MAP (108.7 +/- 16.7 mm Hg, mean +/- SD) and RBC Li+-Na+ countertransport (0.455 +/- 0.147 mmol Li+/l cells.hr) than the larger (81%) group (MAP 93.3 +/- 12.2 mm Hg, RBC Li+-Na+ countertransport 0.247 +/- 0.080 mmol Li+/l cells.hr, p less than 0.0001 for both differences). The relation of MAP to RBC Li+-Na+ countertransport was distinctly different in these two subgroups. In the larger group, we found a weak positive (r = 0.21, p less than 0.0001) correlation for unadjusted values, which was not significant after adjustment. The smaller group, with higher levels of MAP and RBC Li+-Na+ countertransport, showed significant negative correlations for both unadjusted (r = -0.28, p less than 0.008) and adjusted (r = -0.41, p less than 0.0001) values.     

Sodium-lithium countertransport in ambulatory hypertensive and normotensive patients

Numerous studies have reported the mean value for Na+-Li+ countertransport to be increased in red blood cells from patients with essential hypertension. Although concomitant variables including age, body size, national origin, geographic location, gender, and family history of hypertension may affect Na+-Li+ countertransport values, most case-control studies have failed to assess the contribution of these factors to the differences in Na+-Li+ countertransport between hypertensive and normotensive groups. The present study was undertaken to provide estimates of Na+-Li+ countertransport in hypertensive and normotensive subjects after taking into account these potentially confounding sources of variation. In 187 subjects undergoing medical evaluation at the Mayo Clinic, Rochester, MN, the combined effects of variation in age, height, and weight accounted for 20.6% of the interindividual variability in Na+-Li+ countertransport. After adjustment to remove variability due to these concomitants, differences in national origin, region of birth, and place of current residence made no additional contribution to variability in this trait. There was no significant difference in mean adjusted Na+-Li+ countertransport between men and women (0.41 +/- 0.17 vs 0.40 +/- 0.12 [SD] mmol Li efflux/L red blood cells/hr; n = 107). The mean value for adjusted Na+-Li+ countertransport was significantly greater (p less than or equal to 0.001) in subjects with essential hypertension (0.44 +/- 0.15 mmol/L red blood cell/hr; n = 104) compared with normotensive subjects (0.31 +/- 0.07 mmol/L red blood cells/hr; n = 39) or subjects with borderline blood pressure elevation (0.35 +/- 0.11 mmol/L red blood cells/hr; n = 21). Subjects with a family history of hypertension in at least one parent or full sibling had significantly higher (p less than 0.02) Na+-Li+ countertransport values (0.42 +/- 0.16 mmol/L red blood cells/hr; n = 111) than those with no family history of hypertension (0.37 +/- 0.13 mmol/L red blood cells/hr; n = 76). These results suggest that increased mean Na+-Li+ countertransport in hypertensive subjects in this sample cannot be attributed to confounding effects of variation in age, body size, gender, national origin, birthplace, or residence. Forty-eight percent of subjects with essential hypertension had adjusted Na+-Li+ countertransport values above the range observed in normotensive controls.     

Red blood cell sodium-lithium countertransport, blood pressure, and uric acid metabolism in untreated healthy men

The relationship of red blood cell (RBC) Na/Li countertransport to the renal handling of lithium and uric acid was investigated in a sample of 176 untreated men. Subjects in the upper quintile of the Na/Li countertransport distribution (n = 40), compared to those in the two lower quintiles (n = 72), had higher serum uric acid levels (0.34 +/- 0.06 v 0.29 +/- 0.05 mmol/L, P less than 0.001) and systolic blood pressure (131 +/- 19 v 123 +/- 16 mm Hg, P less than 0.02) and slightly lower fractional excretion of uric acid (7.5 +/- 1.5 v 8.4 +/- 2.6%, P less than 0.08). The lithium fractional excretion was not significantly related to either blood pressure or RBC Na/Li countertransport. The altered uric acid metabolism in individuals with high RBC Na/Li countertransport could be the expression of an abnormality of renal tubular function.     

Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension

Alterations in red blood cell (RBC) Na+-K+ pump and Na+-K+ cotransport have been described in essential hypertension. We evaluated Na+-K+ pump and cotransport in 30 hypertensive and 26 normotensive subjects subdivided by race and family history of hypertension using an improved method to examine the kinetics of Na and K effluxes. RBCs were Na-loaded by the nystatin method to five different levels of internal Na with pump determined as ouabain-sensitive Na efflux and cotransport as furosemide-sensitive Na and K efflux. Two kinetic parameters were determined for both transport systems: the apparent affinity for Na (K0.5) and the velocity of efflux at saturating internal Na concentration (Vmax). Mean intracellular Na content in fresh RBCs (mmol/L cells) was higher in black hypertensive (12.6 +/- 1.8 mmol/L cells) and normotensive subjects (10.9 +/- 1.2 mmol/L cells) than in white hypertensive (8.7 +/- 1.0 mmol/L cells) or normotensive subjects (8.5 +/- 0.8 mmol/L cells). The Vmax and K0.5 for pump were not significantly different between study groups. The Vmax for cotransport was elevated in white hypertensive compared with normotensive subjects, but the K0.5 values were similar. Black normotensive and hypertensive subjects displayed a lower Vmax and increased K0.5 for cotransport compared with the white groups. A family history of hypertension had no influence on cotransport kinetics in blacks but did predict white normotensive and hypertensive subjects with low cotransport. The reduction in intracellular Na affinity for cotransport in black subjects may explain their higher intracellular Na in fresh RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between red cell sodium transport, blood pressure, and family history of hypertension

Numerous studies have demonstrated that Na+/Li+ countertransport is increased in erythrocytes from hypertensive patients. Since Na+/Li+ countertransport is conducted through the physiologically occurring Na+/Na+ exchange, we studied the latter pathway in 20 subjects with essential hypertension and 20 normotensive subjects matched for age and sex. Ten hypertensives and six normotensives had a positive family history of hypertension. Ouabain (0.1 mM) and furosemide (0.1 mM) were used to assess the active Na+ efflux and Na+-K+-Cl- pathway. There was no significant difference between hypertensive and normotensive subjects in any of the three pathways studied. Among the 16 subjects with a positive family history of hypertension, the mean value for external Na+-dependent Na+/Na+ exchange was significantly higher than in 24 subjects with no family history of hypertension (0.0457 +/- 0.0337 versus 0.0283 +/- 0.0202; P less than 0.05). This study suggests that an inherited membrane transport defect may exist for Na+/Na+ exchange in families of hypertensive subjects.     

Na+-Li+ countertransport in essential hypertension

Several studies on Na+-Li+ countertransport have reported higher rates in essential hypertensive than in normotensives, with a distribution pattern which is dependent on racial and ethnic background. However, it is not well established whether this abnormality in Na+ transport is associated with an abnormal clinical setting. In the present study we have performed a kinetic analysis of the interaction of the Na+-Li+ countertransport system with internal Na+ in erythrocytes from a sample of 72 essential hypertensives and 30 normotensive controls. A significant increase in mean values of the maximal rate of Li+-stimulated Na+ efflux (Vmax; 375.1 +/- 23.8 versus 213.7 +/- 8.5 mumol/l cells per h; mean +/- s.e.m.; Mann-Whitney test: U = 500; P less than 0.0001), as well as in the apparent affinity constant for internal Na+ (KNa; 10.03 +/- 0.08 versus 6 +/- 0.4 mmol/l cells; Mann-Whitney test: U = 718; P less than 0.0079), were observed in essential hypertensives with respect to normotensives. Using the 95% confidence interval of Vmax in normotensives as the normal range, 29 (40.3%) of the essential hypertensives exhibited values above the normal upper limit. The maximal rate (Vmax) and the internal Na+ content required for half-maximal stimulation (K50%) of Na+-K+ ATPase and outward Na+-K+ cotransport, and the rate constant of Na+ leak (KPNa) in this subset were similar to the values observed in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Red blood cell Na+ transport as a predictor of blood pressure response to Na+ load in young blacks and whites

The present study was designed to investigate the role of abnormalities in red blood cell sodium-potassium-chloride (Na-K-Cl) cotransport and Na+ pump as predictors of the pressor response to chronic oral Na+ loading in young whites and blacks. Subjects were healthy adults from 18 to 23 years of age and included normotensive whites (n = 24) and normotensive blacks (n = 35). Red blood cell transport studies were performed before Na+ loading. The Na+ load consisted of 10 g NaCl daily added to the usual diet. A sodium-sensitive response was defined as an increase of 5 mm Hg or more in mean arterial pressure after the Na+ load; a sodium-insensitive response was a less than 5 mm Hg increase in mean arterial pressure. A sodium-sensitive response occurred in 16% of whites and 57% of blacks. Black subjects have a significantly lower (p less than 0.005) maximal rate of furosemide-sensitive Na+ efflux and a higher Km for cellular Na+ (p less than 0.05) to activate Na-K-Cl cotransport than white subjects. Normotensive blacks with sodium-sensitive blood pressure response had a higher Km (14.4 +/- 6 mmol/l cell, n = 17, mean +/- SD) to activate the cotransport than sodium-insensitive blacks (9.9 +/- 3.7 mmol/l cell, n = 13, p less than 0.001). Normotensive whites had a significantly lower red blood cell Na+ content (p less than 0.05) and a higher maximal rate of cotransport (p less than 0.005) than young normotensive blacks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Red blood cell sodium-lithium countertransport and cardiovascular risk factors in black and white college students

Whites with essential hypertension have high activity of cell membrane sodium-lithium (Na+-Li+) countertransport when compared with normotensives. To determine whether elevated Na+-Li+ countertransport is related to the twofold higher risk of hypertension in US blacks, maximal rates of red blood cell (RBC) Na+-Li+ countertransport were measured in 34 black and 21 white male college students. The race groups were similar in social and physical measurements. Mean Na+-Li+ countertransport activity (mmol Li/RBC per h) was significantly lower in blacks than in whites (0.214 +/- 0.083 versus 0.295 +/- 0.083, P less than 0.001). Countertransport activity was positively correlated with Type A behaviour among whites (r = 0.45, P = 0.039). Other within race correlations between Na+-Li+ countertransport activity and blood pressure and cardiovascular risk factors were generally positive though not significant in whites, whereas they were small or negative in blacks. If Na+-Li+ countertransport has a role in the aetiology of hypertension, it would appear to differ between blacks and whites.     

Erythrocyte Na+/Li+ countertransport and arterial hypertension: data of a cross-sectional population study]

The relation of red blood cell Na+/Li+ countertransport rate to the prevalence of arterial hypertension (AH) and blood pressure was evaluated in 720 individuals aged 23-60 years. In all age groups, the rate of red blood cell Na+/Li+ countertransport was significantly higher in males than in females. Age, alcohol use, obesity in males and age, obesity, and Na+/Li+ countertransport rate in females are factors that predispose to AH, as evidenced by multivariate logistic analysis. The latter parameter is associated with obesity and diastolic blood pressure and unassociated with age, alcohol use, and smoke, as suggested by regression analysis. The distribution of Na+/Li+ countertransport rate values in the population after standardization for ruling out the impact of obesity is erroneous and shifted to the right. This allows it to be presented as a sum of two normal distributions. However, their analysis has failed to reveal statistically significant differences in blood pressure values of AH incidence. The rate of Na+/Li+ countertransport may be regarded as a biological population risk factor for AH, which is, however, less than such factors as age, obesity, and excessive alcohol use.     

Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats

Rat erythrocytes with five different amounts of Na+ content have been prepared by using a new, nondetrimental Na+-loading method (net NaHPO4-influx through the anion carrier). This method allowed the determination of 1) maximal translocation rates and apparent dissociation constants for internal Na+ of the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport and 2) rate constants of Na+ leak in erythrocytes from spontaneously hypertensive rats of the Okamoto strain and Wistar-Kyoto normotensive controls aged 2 to 26 weeks. Two major abnormalities were found in erythrocytes from spontaneously hypertensive rats: 1) a decreased cotransport affinity for internal Na+, which was constantly observed from 2 to 26 weeks of age (mean intracellular Na+ content for half-maximal stimulation of outward Na+-K+ cotransport = 33.1 +/- 7.0 [SD] mmol/L cells in spontaneously hypertensive rats vs 16.7 +/- 4.7 mmol/L cells in Wistar-Kyoto rats; p less than 0.001), and 2) a decreased maximal pump rate in adult (15- to 26-week-old) spontaneously hypertensive as compared with that for age-matched Wistar-Kyoto rats (9-37 vs 34-70 mmol/L cells/hr). Therefore, the low cotransport affinity for internal Na+ appears to be a stable, possibly genetic defect of spontaneously hypertensive rats. Conversely, the decreased maximal pump rate may be a secondary event, possibly reflecting the appearance of endogenous pump inhibitors in the plasma of adult spontaneously hypertensive rats.     

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.     

(Na+ + K+) ATPase inhibitors and intracellular electrolytes in essential hypertension

White blood cell (WBC) Na+ and K+ concentrations, plasma (Na+ + K+)ATPase inhibition and blood pressure were determined in normotensive control subjects and patients with essential hypertension. While the untreated hypertensive group had significantly lower WBC K+ concentrations than the normotensive group (mean +/- SEM, 121.6 +/- 4.4 vs. 134.7 +/- 2.8 mEq/kg, p less than 0.05), no significant difference was observed in WBC Na+ concentrations between the 2 groups. The mean of plasma (Na+ + K+)-ATPase inhibition in untreated hypertensive patients was higher than that in normotensive controls (14.8 +/- 1.7 vs. 7.2 +/- 1.8%, p less than 0.05). The correlations between (Na+ + K+)ATPase inhibition and mean blood pressure and between WBC Na+/K+ ratio and mean blood pressure were significant (r = 0.278, p less than 0.05 and 0.270, p less than 0.05, respectively), but both were weak. However, untreated hypertensive patients with higher (Na+ + K+)ATPase inhibition had significantly higher WBC Na+/K+ ratios than untreated patients with less (Na+ + K+)ATPase inhibition. These results suggest a contribution of plasma (Na+ + K+)ATPase inhibition in the production of high blood pressure in a subset of patients with essential hypertension, which results in altered intracellular K+ concentrations.     

Cation transport markers as predictors of hypertension.

Of the abnormalities of cation transport described in human essential hypertension, an increased maximal activity for red blood cell lithium-sodium (RBC Li(+)-Na+) countertransport is the most appealing candidate for a genetically mediated marker for risk of future hypertension. Population studies have demonstrated that the distribution of values for countertransport can be modelled statistically as a mixture of two overlapping subpopulations. These two modes could result from the action of a single principal determinant, and pedigree-based studies of the genetic transmission of RBC Li(+)-Na+ intertransport activity have suggested that factor may represent the effect of a major monogenic influence segregating in a Mendelian recessive fashion. Although the molecular nature of the proposed genetic lesion underlying high RBC Li(+)-Na+ countertransport is not yet known, a recent linkage study suggests it may be localized to chromosome 4. A preliminary report of a prospective analysis of the predictive value of high RBC Li(+)-Na+ countertransport for future hypertension supports its utility as a premorbid marker for genetic risk of future hypertension. Allelic differences at a genetic locus controlling RBC Li(+)-Na+ countertransport activity may contribute directly to interdividual blood pressure differences or may be linked to other genes that do.     

Outward Na+-K+-Cl- cotransport function in erythrocytes from essential hypertensives

We have performed a kinetic analysis of the interaction of the outward Na+-K+-Cl- cotransport system with intra-cellular Na+ in erythrocytes from 30 normotensive controls and 72 patients with essential hypertension. Neither maximal rate of ouabain-resistant, bumetanide-sensitive sodium efflux (Vmax) nor intracellular Na+ content required for half-maximal stimulation (K50%) were significantly different between normotensives and hypertensives. Nevertheless, using 95% confidence limits of the K50% in the normotensive group as a cut-off point, 21 (29.17%) essential hypertensive patients exhibited values above the upper normal limit of 20.11 mmol/l cells, revealing a decreased apparent affinity of outward Na+-K+-Cl- cotransport for internal Na+ ('Co-' hypertensives). The Vmax of Na+-K+-Cl- cotransport exhibited a great variability among hypertensives but 'Co-' patients tended to have increased values of this parameter when compared with the remaining essential hypertensives (959 +/- 84 vs 652 +/- 39 mumol/l cells/h, P = 0.0024). Mean BP values were significantly lower in the 'Co-' subset (121.4 +/- 1.6 mmHg), compared with the remaining 51 hypertensive patients (126.4 +/- 1.3 mmHg, P = 0.0297). We conclude that an abnormal function of outward Na+-K+-Cl- cotransport is present in 19% to 40% of Spanish patients with essential hypertension and this abnormality may be implicated in the mechanisms of hypertension.