Increased activity of the Mg2+/Na+ exchanger in red blood cells from essential hypertensive patients.

Epidemiological, clinical, and experimental evidence suggests a relation between Mg2+ metabolism and essential hypertension. The aim of the present study was the detection of abnormalities of the erythrocyte Mg2+/Na+ exchanger in essential hypertensive patients. We studied 66 untreated essential hypertensive patients and 36 normotensive control subjects. Maximal efflux rates of total Mg2+ efflux and the Na(+)-dependent and Na(+)-independent components of Mg2+ efflux were determined in Mg(2+)-loaded red blood cells. Mg2+/Na+ exchanger was calculated as the Na(+)-dependent component of the Mg2+ efflux. Mean values of Mg2+/Na+ exchanger were clearly elevated in hypertensive subjects with respect to normotensive control subjects [184.7 +/- 15.7 versus 84.4 +/- 6 mumol(L.cell.h)-1; P < .001]. This elevation was due primarily to the increased total Mg2+ efflux [324.2 +/- 21.9 versus 257.9 +/- 17.3 mumol(L.cell.h)-1; P < .05], whereas the Na(+)-independent component was not significantly different between the groups [154.5 +/- 11.8 versus 173.4 +/- 15.5 mumol(L.cell.h)-1; P = NS]. Moreover, total erythrocyte Mg2+ content was slightly reduced in hypertensive patients with respect to normotensive control subjects (1.84 +/- 0.04 versus 2.07 +/- 0.04 mmol/L.cell; P < .001). Using the 99% confidence limits of the normotensive population as the normal range, 30 (45.5%) hypertensive subjects showed values of Mg2+/Na+ exchanger higher than 160 mumol(L.cell.h)-1. The Mg2+/Na+ exchanger was inversely correlated with basal intraerythrocyte Mg2+ content (r = -.323; P = .001). From a clinical point of view, we found a positive correlation between diastolic blood pressure values and Mg2+/Na+ exchanger (r = .246; P < .05) in the sample of essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte sodium transport, intraplatelet pH, and calcium concentration in salt-sensitive hypertension.

We evaluated changes in erythrocyte sodium transport systems, platelet pH, and calcium concentration induced by low and high salt intakes in a group of 50 essential hypertensive patients classified on the basis of their salt sensitivity. Patients received a standard diet with 20 mmol NaCl daily for 2 weeks supplemented in a single-blind fashion by placebo tablets the first 7 days and NaCl tablets the following 7 days. Salt sensitivity, defined as a significant rise (P <.05) in 24-hour mean blood pressure obtained by ambulatory blood pressure monitoring, was diagnosed in 22 (44%) patients. The remaining 28 (56%) were considered to have salt-resistant hypertension. In the entire group of hypertensive patients, high salt intake promoted a significant increase (P <.05) in the maximal rate of erythrocyte NA(+)-Li(+) countertransport (from 271 +/- 19 to 327 +/- 18 microM/(L cells/h) and of the Na(+)-dependent HCO3(-)-CL(-) exchanger (from 946 +/- 58 to 1237 +/- 92 microM/L cells/h) as well as in platelet pH (from 7.15+/-0 0.01 to 7.19+/-0.02 and calcium concentration (from 49+/-2 to 57 +/-2 nmol/L). Depending on salt sensitivity, high salt intake promoted opposing changes in some of the sodium transport systems studied. Salt-sensitive patients increased the maximal rate of the erythrocyte Na(+)-K(+) pump (fom 7.0 +/- 0.4 to 8.8 +/- 0.4 mmol/(L cells/h), Na(+)-K(+)-Cl(-) cotransport (from 416 +/- 37 to 612 +/- 41 micromol/(L cells/h), Na(+)-Li(+) countertransport (from 248 +/- 20 to 389 +/- 17 micromol/(L cells/h) at the end of the high salt period. Conversely, salt-resistant patients decreased the Na(+)-K(+) pump (from 8.0 +/- 0.4 to 6.9 +/- 0.3 mmol/(L cells/h) and Na(+)-K(+)-Cl(-) cotransport (from 578 +/- 53 to 481 +/- 43 micromol/(L cells/h). We conclude that modulation of erythrocyte sodium transport systems by high salt intake depends on salt sensitivity. The Na(+)-K(+) pump, Na(+)-K(+)-Cl(-) cotransport, and Na(+)-Li(+) countertransport increase in salt-sensitive patients, whereas the activity of these sodium transport systems tends to decrease in salt-resistant patients. Independent of salt sensitivity, high salt intake promotes a significant increase in the erythrocyte Na(+)-dependent HCO3(-)-Cl(-) exchanger, platelet pH, and calcium concentration in essential hypertensive patients.

Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring.

Several studies have shown that cessation of alcohol drinking reduces blood pressure (BP). However, attempts to reproduce these findings by ambulatory BP monitoring (ABPM) have shown inconsistent results. The aim of the present study was to assess the effect of 1 month of proven abstinence from alcohol on the 24-hour BP profile in heavy alcohol drinkers. Forty-two men who were heavy drinkers (>100 g of pure ethanol per day) were consecutively admitted to a general ward for voluntary alcohol detoxification. On the day of admission, they received a total dose of 2 g/kg of ethanol diluted in orange juice in 5 divided doses, and a 24-hour ABPM was performed. A new 24-hour BP monitoring in the same environmental conditions was performed after 1 month of proven alcohol abstinence while the subjects were receiving the same amount of fluid but without the addition of alcohol. After 1 month of proven alcohol abstinence, BP and heart rate (HR) significantly decreased. The reduction was 7.2 mm Hg for 24-hour systolic BP (SBP) (95% CI, 4.5 to 9.9), 6.6 mm Hg for 24-hour diastolic BP (DBP) (95% CI, 4.2 to 9.0), and 7.9 bpm for HR (95% CI, 5.1 to 10.7). The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence. Abstinence did not modify either the long-term BP variability, assessed by SD of 24-hour BP, or its circadian profile. We conclude that abstinence in heavy alcohol drinkers significantly reduces BP assessed by 24-hour ABPM and that this reduction is clinically relevant. These results show that heavy alcohol consumption has an important effect on BP, and thus cessation of alcohol consumption must be recommended as a priority for hypertensive alcohol drinkers.

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)

Disturbances of transmembranous sodium transport systems induced by ethanol in human erythrocytes. An approach to the pressor effect of alcohol.

Several epidemiological and clinical studies have established a clear association between alcohol consumption and hypertension. The mechanism of the pressor effect of ethanol is not well understood. We studied the in vitro effects of increasing amounts of ethanol on different Na+ transport systems from human erythrocytes. Ethanol at concentrations higher than 32 mmol/L stimulated ouabain-sensitive Na+ efflux, the Na+ efflux depending on the Na+:Li+ countertransport and Na+ leak. At the same concentrations, ethanol inhibited bumetanide-sensitive Na+ efflux. We conclude that, with the exception of Na+-K+ pump, alcohol-induced alterations and those observed in erythrocytes from essential hypertensives may overlap. Therefore, alcohol consumption could potentiate those genetic abnormalities of Na+ transport and contribute to the pathogenesis of essential hypertension.

Assessment of salt sensitivity in essential hypertension by 24-h ambulatory blood pressure monitoring.

We used ambulatory blood pressure monitoring (ABPM) in the assessment of salt sensitivity in 40 essential hypertensive patients, comparing 24-h mean blood pressure during 7 days of low salt (20 mmol NaCl/day) and high salt (260 mmol NaCl/day) intake. Salt sensitivity was diagnosed in 18 essential hypertensive patients (45%), each of them showing a significant increase in mean blood pressure (P < .05) from low to high salt diet. Salt-sensitive patients exhibited a high-salt-dependent increase in all blood pressure parameters including 24-h systolic, mean, diastolic blood pressure, blood pressure load, area under the curve, and awake and asleep blood pressure values. These patients exhibited a nondipper profile on both low-salt and high-salt diets. Salt-resistant patients (55%) showed a decrease in awake, and an increase in asleep blood pressure values after high salt intake, thus tending to flatten the circadian blood pressure profile. We conclude that ABPM is a useful method to assess salt sensitivity. In salt-resistant patients high salt intake induces a significant increase in asleep blood pressure with no significant changes in 24-h blood pressure, promoting a flattened blood pressure curve and tending to transform a dipper into a nondipper profile, which could have important implications in end-organ damage.

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.

Increased left ventricular mass in salt-sensitive hypertensive patients.

Clinical, biochemical and echocardiographic characteristics were evaluated from 50 essential hypertensive patients classified asccording to their salt-sensitivity status. Salt-sensitive hypertension was diagnosed by means of ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20 mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake. The remaining 28 (56%) patients were considered as having salt-resistant hypertension. Compared with salt-resistant patients, salt-sensitive ones showed an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and posterior wall thickness (P = 0.0026), without differences in the internal diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed in the salt-sensitive, compared with the salt-resistant hypertensive patients. Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose, creatinine and uric acid did not differ between salt-sensitive and salt-resistant patients. We conclude that, at the same level of BP, salt-sensitive patients exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid profile. These two aspects may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.

Microalbuminuria in essential hypertension: clinical and biochemical profile.

This study aims to evaluate the clinical and biochemical profile associated with the presence of microalbuminuria in a group of essential hypertensive patients referred to a hypertension clinic. A total of 188 non-diabetic, untreated essential hypertensive patients (100 men, 88 women) aged 55.8 +/- 11.7 years are studied. Urinary albumin excretion was determined in two 24-h urine collections. Clinical and biochemical evaluations and 24-h ambulatory blood pressure (BP) monitoring were performed at baseline. Forty-two patients (22.3%) showed an increased urinary albumin excretion rate (20-200 micrograms/min). These patients showed significantly higher values (P < 0.01) for 24-h, daytime and night-time systolic and diastolic BP, compared with essential hypertensives with normal urinary albumin excretion. However, nocturnal reduction in BP did not differ between the groups. Furthermore, patients with microalbuminuria showed significantly higher (P < 0.01) creatinine, serum uric acid and triglycerides, as well as lower high-density lipoprotein (HDL)-cholesterol. In a multiple logistic regression analysis, a 24-h systolic BP > 140 mmHg (odds ratio: 3.19; 95% confidence interval [CI 95%]: 1.44-7.06) and a serum creatinine > 88 mumol/L (odds ratio: 3.08; CI 95%: 1.39-6.84) were the two factors associated independently with increased urinary albumin excretion. We conclude that, in essential hypertensive patients, the presence of microalbuminuria is associated with elevated BP, but not with its circadian pattern. Likewise, microalbuminuria is associated with the degree of renal impairment, and with increased uric acid and triglycerides and decreased HDL-cholesterol.

[Calcium pump changes in patients with essential arterial hypertension]. / Alteraciones de la bomba de calcio en pacientes con hipertensión arterial esencial.

BACKGROUND: Transmembrane Ca2+ fluxes are mediated, at least in part, by the Ca(2+)-dependent ATPase. Thus, genetic or acquired abnormalities of this pump could explain the increase in free cytosolic Ca2+ content that has been observed in essential hypertensive patients. PATIENTS AND METHODS: We carried out a kinetic study of the Ca2+ pump in intact erythrocytes from 49 essential hypertensive patients and 27 normotensive healthy persons. We used Sr2+ as a calcium analogue to measure Ca2+ fluxes dependent of the Ca2+ pump. The intracellular concentrations of Sr2+ and Ca2+ were modified using the A-23187 ionophore in a Ringer isotonic solution. RESULTS: Hypertensive patients showed a significant increase of the maximal efflux rate for Sr2+ (Vmax) with respect to controls (6.6 [2.3] vs 5.2 [1.6] mmol/l cel/h; p = 0.006). Mean values of apparent dissociation constants for intracellular Ca2+ (KCa) were also increased in essential hypertensives (80.36 [53.46] vs 55.25 [15.13] mumol/l cel; p = 0.06). A significant correlation between Vmax and age (r = 0.342; p = 0.016), and serum creatinine (r = 0.446; p = 0.001) was observed. The KCa only correlated with serum creatinine (r = 0.402; p = 0.004). Using the KCa confidence interval of 99% as the higher normal limit, patients were segregated into two subgroups depending on normal KCa values (33 patients, 67.3%) or increased KCa values (16 patients, 32.6%). Age (50.8 [13.5] vs 43 [10.2] years; p = 0.02), serum creatinine (1.13 [0.17] vs 0.95 [0.17] mg/dl; p = 0.001) and serum uric acid (7.27 [3.32] vs 6.14 [1.49] mg/dl; p = 0.04) were higher in patients with increased KCa. Finally, patients with increased KCa also showed increased values of Vmax (9.13 [2.02] vs 5.38 [12.81] mmol/l cel/h; p < 0.0001). CONCLUSIONS: Essential hypertensive patients are heterogeneous regarding ion transport abnormalities, only affecting subgroups of hypertensive patients. We have observed abnormalities of the Ca(2+)-dependent ATPase in 33% of essential hypertensive patients. These patients are older and tend to exhibit higher values of serum creatinine and uric acid.

[Prevalence of lipid disorders and their course after blood pressure control in essential arterial hypertension]. / Prevalencia de los trastornos lipídicos y su evolución tras el control tensional en la hipertensión arterial esencial.

BACKGROUND: Arterial hypertension and hyperlipidemia are the principal factors of cardiovascular risk with an association which appears to obey common pathogenic bonds. In the present study the initial prevalence of hypercholesterolemia and hypertriglyceridemia was determined in a sample of essential hypertensives and the long term effect of different antihypertensive treatments on lipid metabolism has been analyzed. METHODS: Total cholesterol, its LDL and HDL fractions and plasmatic triglycerides were determined in a sample of 158 hypertensive patients prior to the initiation of antihypertensive treatment and following one year of normotension. RESULTS: The initial prevalence of lipid disturbances was of 47% (isolated hypercholesterolemia 17%, isolated hypertriglyceridemia 14% and mixed anomalies 16%). After one year of tension control the initial prevalence was not modified. In the patients controlled with a low sodium diet a decrease in total cholesterol and an increase in cholesterol-HDL were observed in those treated with atenolol, and a decrease in cholesterol-LDL was seen in those receiving captopril. The group treated with nifedipin presented no significant variations of the lipid profile. CONCLUSIONS: The prevalence of lipid disturbances is greater among the hypertensive patient than in the general population. The rational treatment of a hypertensive patient must not only regard blood pressure figures but also control the other risk factors since the drugs commonly used in the treatment of arterial hypertension generally demonstrate a neutral effect on lipid metabolism.

[The clinical profile of hypertensive patients can predict the need for combining a second or third drug with atenolol in the initial treatment of light and moderate essential arterial hypertension]. / El perfil clínico de los pacientes hipertensos puede predecir la necesidad de asociar un segundo o tercer fármaco al atenolol en el tratamiento inicial de la hipertensión arterial esencial leve y moderada.

In this study the clinical, biological, radiologic, electrocardiographic, and hormonal characteristics of 80 patients with slight or moderate essential arterial hypertension in whom the treatment with atenolol alone or associated with chlorthalidone or with a third agent normalized the arterial pressure during a period of one year, are revised. Atenolol given alone at the dose of 50 to 100 mg per day normalized the blood tension in 44 (55%) patients, in 26 cases (32.5%) the association of chlorthalidone 25 mg/day was required, and in the remaining 10 patients (12.5%) a third pharmacologic agent was needed. Patients who required the association of three agents (group C) had systolic arterial pressures significantly higher than those observed in patients treated with atenolol alone (group A) (176.6 +/- 14.3 vs 161.4 +/- 12.9 mmHg, p less than 0.01) and higher to those measured in patients who required the association of chlorthalidone (group B) (176.6 +/- 14.3 vs 162.8 +/- 15 mmHg, p less than 0.05). On the other hand the 44 hypertensive patients controlled with monotherapy showed a lower incidence of cardiovascular complications (6.8% in group A, 38.5% in group B, and 30% in group C, p = 0.0042), they required acute treatment for hypertensive crisis (34.1% in group A, 73.1% in group B, and 66.7% in group C, p = 0.0041), and they showed electrocardiographic signs of left ventricular hypertrophy or overload (26.2% in group A, 60% in group B, and 42.9% in group C, p = 0.0228).(ABSTRACT TRUNCATED AT 250 WORDS)

Obesity-related eating behaviours in the adult population of Spain, 2008-2010.

Knowledge of the socio-demographic distribution of eating behaviours can aid our understanding of their contribution to the obesity epidemic and help to address healthy eating interventions to those who can benefit most. This cross-sectional study assessed the frequency of self-reported eating behaviours among 11,603 individuals representative of the non-institutionalized Spanish population aged ≥ 18 years in the period 2008-2010. In the adult population of Spain, 24.3% had lunch and 18.2% had dinner away from home >3 times per month. About three-fourths of adults did not plan the amount of food to be eaten, and did not choose light foods and/or skim dairy products. Also, 26% did not trim visible fat from meat, and 74.7% usually ate while watching television. Compared with individuals with primary or less education, those with university studies were more likely to remove fat from meat (age- and sex-adjusted odds ratio [aOR] 1.25; 95% confidence interval [CI] 1.08-1.44), and to choose light food and/or skim dairy (aOR 1.50; 95% CI 1.30-1.77), and less likely to eat while watching television (aOR 0.54; 95% CI 0.47-0.63). In conclusion, the prevalence of several obesity-related eating behaviours is high in Spain, which indicates a deficient implementation of dietary guidelines. Socioeconomic inequalities in eating behaviours should also be addressed.

Abnormal erythrocyte sodium leak in a subset of essential hypertensive patients.

We measured the ouabain- and bumetanide-resistant Na+ efflux in Mg2+-sucrose medium (passive Na+ leak) in erythrocytes from 30 normotensive controls and 72 essential hypertensive patients. The mean values (+/- SEM) of the rate constant of Na+ leak (kpNa) were not significantly different between normotensives and hypertensives. Nevertheless, using the 95% confidence limits of the kpNa (in 10(-3).h-1) in the normotensive group as a cut-off point, 7 (9.7%) essential hypertensives exhibited increased values (58.96 +/- 10.12) when compared with the other 65 patients (23.86 +/- 0.74). revealing increased passive Na+ permeability in the former (leak "+" hypertensives). Na+ fluxes depending on the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport were also measured in fresh erythrocytes from the same 72 patients. Three of them (4.2%) exhibited decreased values of ouabain-sensitive Na+ efflux and 6 (8.3%) of bumetanide-sensitive Na+ efflux, while 8 patients (11.1%) showed increased values of Li+-stimulated Na+ efflux and, finally, 48 patients (59.7%) did not present any evident abnormality in these Na+ transport systems. No differences were observed between leak "+" hypertensives and the remaining 65 patients when both basal erythrocyte Na+ content and clinical parameters of hypertension were compared. However, Na+ efflux depending on the outward Na+-K+ cotransport was significantly higher in the leak "+" hypertensive subset (299.43 +/- 43.18 vs 181.52 +/- 10.76 mumol.(l cells.h)-1; P = 0.0078), suggesting a compensatory phenomenon. Enhancement of Na+ permeability detected in 3% to 16% of essential hypertensives may be implicated in the pathogenesis of primary hypertension.

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.

Clinical profiles and erythrocyte Na+ transport abnormalities of four major types of primary hypertension in Spain.

The interaction of three different Na+ transport systems (Na+-K+ pump, Na+-K+ cotransport and Na+-Li+ countertransport), with internal Na+ and the passive Na+ leaks, were measured in erythrocytes from 72 Spanish, essential hypertensive patients and 30 normotensive controls. According to the observed abnormalities in Na+ transport pathways, 93.1% of the patients were classified into the following subsets: 12 (16.7%) exhibited a decreased apparent affinity of Na+-K+ pump for internal Na+ (Pump "-" hypertensives); 20 (27.7%) showed a decreased apparent affinity of Na+-K+ cotransport for internal Na+ (Co "-" hypertensives); 27 (37.5%) showed an accelerated Na+-Li+ countertransport (Counter "+" hypertensives); and 5 (6.9%) exhibited an increased rate constant of passive Na+ leaks (Leak "+" hypertensives). Finally, 5 patients (6.9%) did not show any abnormality in their Na+ transport systems and 3 exhibited more than one. Moreover, distinctive clinical features were recognize in Co "-" and Counter "+" subsets. Blood pressure values were lower in the former and, conversely, Counter "+" hypertensives showed a higher prevalence of moderate or severe hypertension (65.5% vs. 32.6%; P = 0.0059) and higher values of stimulated plasma renin activity (1.63 +/- 0.52 vs. 0.81 +/- 0.15; P = 0.0443). Our results confirm the heterogeneity of Na+ transport abnormalities in essential hypertension and suggest that these subsets of hypertensives could represent clinical entities.