Intra-erythrocyte cation concentrations in relation to the C1797T beta-adducin polymorphism in a general population.

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na(+) [iNa], K(+) [iK] and Mg(2+) [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy-Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R(2)=0.128) increased with age and serum Na(+), but decreased with serum total calcium and the daily intake of alcohol. iMg (R(2)=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P

Arginine-aminopeptidase in rat cardiac fibroblastic cells participates in angiotensin peptide turnover.

OBJECTIVE: The aim of the present study was to elucidate the presence in rat cardiac fibroblastic cells of arginine-aminopeptidase and its involvement in the hydrolysis of angiotensin peptides. METHODS: Peptidase activity was measured as hydrolysis of the synthetic substrates, aryl-p-nitroanilides. Immunoblottings were performed with antibodies to aminopeptidase B and Glyceraldehyde-3-phosphate dehydrogenase. RESULTS: Arginine-aminopeptidase found in cardiac fibroblasts (Fb) was arginine and lysine specific, sensitive to various aminopeptidase (AP) inhibitors and to the inhibitor of metalloproteases, 1.10-phenatroline. Experiments with arphamenine A, a specific inhibitor of aminopeptidase B, have shown the presence of two Arginine-aminopeptidase activities: arphamenine-sensitive: chloride-stimulated Arginine-aminopeptidase, and arphamenine-insensitive: chloride-insensitive Arginine-aminopeptidase. Transforming growth factor-beta1 stimulated both Arginine-aminopeptidase activities by approximately threefold. Immunoblot with an antibody specific to rat aminopeptidase B has revealed that arphamenine-sensitive: chloride stimulated aminopeptidase is aminopeptidase B. Arginine-p-nitroanilide hydrolysis was significantly inhibited by angiotensin peptides such as angiotensin (1-10), (1-8), (1-7), (1-4), (5-8), (4-8), (3-8), and (2-8) at the concentration of 50 micromol/l which was fourfold less than the Arginine-p-nitroanilide concentration. CONCLUSIONS: Our data show that chloride-insensitive Arginine-aminopeptidase could contribute to the hydrolysis of all studied angiotensin peptides in concert with other peptidases present in fibroblasts. Some of the peptides could probably not be hydrolyzed by Arginine-aminopeptidase. Instead, they could be first hydrolyzed by another peptidase in fibroblasts and the product of this hydrolysis could be a substrate for Arginine-aminopeptidase. The data obtained suggest that Arginine-aminopeptidase could perform processing of angiotensin peptides in the myocardium and participate in processes regulated by angiotensins such as fibrosis.

Intracellular sodium and the response to nitrendipine or atenolol in African blacks.

The relationship between the hypotensive effect of nitrendipine (N), 20 mg/day (n = 17), or atenolol (A), 100 mg/day (n = 17), and the erythrocyte sodium [( Na]i) and potassium [( K]i) concentrations was investigated in hypertensive African blacks during a randomized double-blind study. After 6 weeks, both treatments significantly reduced supine and standing blood pressures; however, the magnitude of the decrease in supine systolic (-22.0 +/- 2.0 vs -12.1 +/- 3.4 mm Hg) and diastolic (-14.1 +/- 1.3 vs -7.6 +/- 2.1 mm Hg) pressures and in standing diastolic pressure (-16.0 +/- 1.7 vs -9.2 +/- 2.0 mm Hg) was more pronounced (p less than 0.05) in the N-treated than in the A-treated group. Pulse rate, plasma aldosterone, and plasma renin activity were lower (p less than 0.05) in the A-treated patients. Neither treatment had significant influence on [Na]i, [K]i, or ouabain-sensitive sodium efflux. The N-induced changes in supine systolic and diastolic pressure correlated (p less than 0.05) with age (r = -0.65 and r = -0.58, respectively) and pretreatment plasma renin activity (r = 0.71). Multiple regression analysis demonstrated a negative association between pretrial [Na]i and the change in systolic pressure during N treatment that was independent of age, pretreatment blood pressure, and change in pulse rate. Age and the change in supine pulse rate were also independently correlated with the change in diastolic pressure during N treatment. The results show a greater antihypertensive efficacy of N than A in the patients entered in this study and suggest that a higher intracellular sodium concentration could predict a better hypotensive response to N.

Dose response in captopril therapy of hypertension.

Dose-response curves of blood pressure and of the biochemical components of the renin-angiotensin-aldosterone system were determined during long-term treatment with captopril in 21 hypertensive patients. Captopril was given in biweekly, doubling doses starting with 25 mg 3 times a day until control of blood pressure was achieved or a total daily dosage of 600 mg was reached. Recumbent and standing systolic and diastolic blood pressure fell on 75 mg captopril daily. Increasing the captopril dose did not induce further significant hypotensive effects. The pretreatment level of plasma renin activity (PRA) was a poor predictor of the hypotensive effect of captopril. The rises in PRA and plasma angiotensin I level (PA I) and the decrease in plasma angiotensin II level (PA II) and plasma aldosterone level (PAC) provide biochemical evidence for angiotensin-converting enzyme (ACE) inhibition in vivo. These effects were present on daily doses of 75 to 150 mg captopril.

Effects of tibalosine, a new alpha-adrenoceptor antagonist, in essential hypertension.

Tibalosine is a phenylethylamine derivative known to lower arterial pressure in hypertensive animal models. In a double-blind cross-over study, 12 patients with essential hypertension, on a constant sodium intake, received placebo and tibalosine, 150 mg daily. Standing (-5.5/-6.0 mm Hg) and supine (-8.5/-7.5 mm Hg) blood pressure and standing (-7.0 bmp) and supine (-7.5 bpm) pulse rate were reduced by tibalosine. Plasma renin activity (-0.41 ng/ml/hr) and plasma angiotensin 1 (-47 pg/ml) and angiotensin II (-3.0 pg/ml) levels decreased. There were no significant changes observed in plasma aldosterone or in the urinary excretion of aldosterone, kallikrein, or prostaglandin E2, F2 alpha, and F alpha metabolites. During tibalosine treatment, creatinine clearance decreased by 20 ml/min and serum creatinine rose by 0.04 mg/100 ml. The increase in serum sodium by 0.05 mmol/l was not accompanied by significant changes in body weight. There were small, but significant reductions in hemoglobin (-0.4 gm/100 ml), hematocrit (-1.5%), and erythrocyte count (-0.15 X 10(6) cells/mm3) during tibalosine intake, while blood glucose rose by 4.0 mg/100 ml. Apart from a slight tranquilizing effect in two anxious patients, no obvious sedation was observed. Subjective complaints were as frequent during placebo as during active treatment periods.

Relationship between blood level of atenolol and pharmacologic effect.

Thirty-five hypertensive patients were treated with atenolol in weekly increasing doses (25, 50, 100, and 200 mg thrice daily). Factors determining the blood level of the drug were studied along with the relationship between blood level, the degree of cardiac beta blockade, and the antihypertensive effect of the drug. The blood level obtained varied with the daily dose, the time of blood sampling during the day, the body weight, and the creatinine clearance. The degree of beta blockade was assessed by measuring maximum-exercise tachycardia and was correlated with the blood level of atenolol. The reduction of the maximum exercise heart rate was independent of age. The hypotensive effect was not closely correlated with the blood level. Three days after the termination of long-term atenolol treatment, blood levels and beta blockage were still detectable.

Calcium entry blockade or beta-blockade in long-term management of hypertension in blacks.

The long-term efficacy of nitrendipine and acebutolol was assessed during a 40-week double-blind randomized trial in 60 hypertensive blacks. Nitrendipine (mean dose 32 mg/day) and acebutolol (414 mg/day) were administered in monotherapy in increasing dosage and mefruside was added in patients not controlled by monotherapy. The recumbent and standing blood pressures were reduced (P less than 0.01 or less) during monotherapy with nitrendipine and acebutolol, but the magnitude of blood pressure reduction was greater (P less than 0.05 or less) during nitrendipine dosing. Pulse rate decreased (P less than 0.01) during acebutolol whereas nitrendipine induced a nonsignificant increase. Both treatments induced no changes in serum electrolytes, creatinine, urea, uric acid, lipids, plasma renin activity, and plasma and urinary aldosterone. The overall incidence of side effects was similar with both treatments but four patients discontinued nitrendipine because of headache. The addition of mefruside to nitrendipine or acebutolol produced a further fall of blood pressure in patients not controlled with monotherapy. Monotherapy with nitrendipine or acebutolol offers an effective, safe first-line antihypertensive treatment in blacks entered in this study; with the described dosages and therapeutic schedule, nitrendipine was somewhat more effective than acebutolol.

Salt and blood pressure in community-based intervention trials.

This article reviews community-based salt intervention trials. In the Belgian Salt Intervention Trial, a controlled 5-y intervention in two Belgian towns resulted in a reduction in urinary sodium of 17 mmol/24 h (P < 0.001) in adult (aged > or = 20 y) women in the intervention town, which differed from the concurrent trend (an increase of 8 mmol/24 h) in the control town (P = 0.01). However, both systolic (-7.5 compared with -7.9 mm Hg) and diastolic (-2.3 compared with -3.0 mm Hg) pressures declined to the same extent in women of the two towns. In adult men in the intervention town, decreases were observed in urinary sodium (-12 mmol/24 h) and in systolic (-5.6 mm Hg) and diastolic (-2.4 mm Hg) blood pressures, but these trends were the same in the control town (-12 mmol/24 h, -4.9 mm Hg, and 0.2 mm Hg, respectively). The Belgian study and the four other community-based salt intervention trials reviewed show that, in general, salt intake in the long-run cannot be restricted below 5 g/24 h. More moderate salt restriction may constitute a more realistic goal, but its influence on blood pressure in the community at large is probably trivial.

Dietary calcium, blood pressure and cell membrane cation transport systems in males.

OBJECTIVE: A double-blind, placebo-controlled parallel-group study was conducted on the effect of a high level of daily oral calcium supplementation (1 g elemental calcium given twice a day for 16 weeks) in normal male subjects on blood pressure, intracellular cationic concentrations and transmembrane cation transport systems, plasma total and ionized calcium, and calciotropic hormones. METHODS: After a 1-month run-in period with a limited intake of dairy products, the 32 subjects were allocated to a placebo or a calcium group. Placebo or 1 g elemental calcium was administered twice a day, in the morning and evening, for 16 weeks. All subjects were investigated at baseline and after 1, 2, 4, 8 and 16 weeks of placebo or calcium administration. RESULTS: Compared with the placebo group, standing systolic blood pressure was decreased in the calcium group, whereas the standing diastolic blood pressure tended to decrease. The changes in supine systolic and diastolic blood pressure did not differ between the placebo and calcium groups. Decreased intra-erythrocyte and intraplatelet sodium and calcium concentrations, an increased activity of platelet and erythrocyte sodium-pump activity and a reduced membrane cholesterol content were observed in the calcium-treated subjects. Erythrocyte membrane surface and core microviscosity, however, did not change during calcium supplementation. Oral calcium supplementation in these men was accompanied by a reduction in the plasma concentrations of intact parathormone and 1,25-dihydroxyvitamin D3, and an increase in 24 h urinary calcium excretion, but no change in the plasma total calcium concentration, serum ionized calcium level, or plasma phosphate or 25-hydroxyvitamin D3. The intra-erythrocyte and intraplatelet potassium and magnesium concentrations as well as the activities of the erythrocyte Na,Li-countertransporter and Na,K-cotransporter, and sodium and potassium leakage did not change during calcium administration. CONCLUSIONS: The lowering of standing blood pressure seen in men with a high calcium intake is accompanied by a decrease in cytosolic free platelet calcium and total erythrocyte calcium, by a reduction in intraplatelet and intra-erythrocyte sodium concentration and erythrocyte membrane cholesterol and by an increase in the activity of the erythrocyte and platelet sodium-pump.

Cytosolic calcium changes induced by angiotensin II in human peripheral blood mononuclear cells are mediated via angiotensin II subtype 1 receptors.

OBJECTIVE: To determine the effects of angiotensin II (AII) (1-8) on cytosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC). We also assessed the effect of the AII analogues AII (2-8), AII (3-8) and AII (4-8) on the cytosolic free-calcium concentration in human PBMC. METHODS: The cytosolic free-calcium concentration was assayed in human peripheral blood mononuclear cells by measuring the fluorescence of fura-2 entrapped by these cells. RESULTS: Administration of AII caused a concentration-dependent increase in the cytosolic free-calcium concentration in human peripheral blood mononuclear cells with a half-maximal increase at 5 x 10(-8) mol/l. Also administration of the heptapeptide AII (2-8) increased the intracellular free-calcium concentration in human PBMC, whereas AII (3-8) and AII (4-8) had no effect. The AII (1-8)-induced rise in cytosolic free-calcium concentration was blocked completely by losartan but not by P-186. CONCLUSION: Our data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PBMC are AT1 receptor-mediated since they were abolished by the specific AII AT1 receptor antagonist losartan but not by the specific angiotensin subtype 2 receptor antagonist P-186.

Activation by calcium of erythrocyte Na+/H+ exchange in men.

OBJECTIVE: To determine whether protein kinase C is necessary for the calcium activation of the Na+/H+ exchange in human erythrocytes by studying activation by calcium of erythrocyte Na+/H+ exchange in control cells, in protein kinase C-depleted cells after downregulation of protein kinase C with phorbol-12-myristate-13-acetate and in cells that had been treated beforehand with phorbol-12-myristate-13-acetate with and without the calpain inhibitor E-64d. METHODS: Erythrocyte Na+/H+ exchange was measured by determining the initial rates of the influx of Na+ into Na+-depleted, acid loaded cells. The effects of various concentrations (0-1 mmol/l) of CaCl2 and the effects of 1 mmol/l CaCl2 on activation of the intracellular pH and on the external Na+ activation of Na+/H+ exchange were studied. The effects of 1 mmol/l CaCl2 on Na+/H+ exchange in control cells and cells that had been incubated beforehand with and without 1 micromol/l phorbol-12-myristate-13-acetate and with E-64d and 1 micromol/l phorbol-12-myristate-13-acetate for 1, 2, 3 and 24 h were also investigated. RESULTS: Addition of Ca2+ to a concentration in the range 0-1 mmol/l in the presence of calcimycin resulted in stimulation of Na+/H+ exchange: 1 mmol/l CaCl2 increased (P< 0.001) the erythrocyte Na+/H+ exchange by 74%. Calcium increased the maximum rate for activations by intracellular pH and by external Na+ of Na+/H+ exchange, whereas it did not affect the Michaelis-Menten constants for activation by intracellular H+ and external Na+. However, calcium did not activate the Na+/H+ exchange in protein kinase C downregulated erythrocytes and administration of the calpain inhibitor E-64d could not prevent this inactivation. CONCLUSION: Our data indicate that protein kinase C is necessary for the activation by calcium of the erythrocyte Na+/H+ exchange.

Reduction of left ventricular mass by antihypertensive treatment does not improve exercise performance in essential hypertension.

OBJECTIVE: To test the hypothesis that a reduction in left ventricular mass by long-term antihypertensive treatment, possibly associated with an improvement of diastolic function, would increase exercise performance in patients with essential hypertension. DESIGNS After a placebo run-in period, 27 patients with essential hypertension World Health Organization stages I and II were assigned randomly to 6-month double-blind treatment with either a diuretic (hydrochlorothiazide plus triamterene) or a converting enzyme inhibitor (trandolapril), to which the calcium antagonist amlodipine could be added after 3 months if required for better blood pressure control. METHOD: Investigations included clinic and ambulatory blood pressure measurements, left ventricular imaging and transmitral Doppler echocardiography and graded maximal exercise testing on the bicycle ergometer with respiratory gas analysis. RESULTS: Six-month antihypertensive therapy, which caused significant (P < 0.001) reductions in blood pressure (by 16% for clinic pressure) and in left ventricular mass (by 13%), but without convincing evidence of improved diastolic function, did not affect exercise performance or peak oxygen uptake. The influence on clinic, exercise and ambulatory blood pressures and on the peak oxygen uptake was similar in the two treatment arms but left ventricular wall thickness decreased to a greater extent in the trandolapril group (P< 0.05 at 3 months and P= 0.06 at 6 months). CONCLUSIONS: Regression of left ventricular mass caused by 6-month antihypertensive therapy does not improve exercise performance of patients with essential hypertension.

Effect of antihypertensive medication on endurance exercise capacity in hypertensive sportsmen.

Beta-adrenoceptor blockade can influence exercise capacity negatively, but data on the effect of converting enzyme inhibition and of calcium entry blockade on exercise capacity in hypertensive sportsmen are scarce. This report deals with the effect of the various types of antihypertensive medication on endurance exercise capacity in 14 hypertensive sportsmen, aged 39 +/- 3 years and weighing 73 +/- 2 kg (mean +/- s.e.m.). The patients were treated for 3 weeks with either placebo, atenolol (50 mg/day) enalapril (10 mg/day) or verapamil (240 mg/day) following a double-blind randomized cross-over design. At the end of each treatment period, they performed an endurance exercise test on the bicycle until exhaustion at 70% of their previously determined exercise capacity. Venous blood was sampled before and after exercise. In comparison with placebo, total exercise duration was not affected by enalapril (-3 +/- 7%) or verapamil (-7 +/- 11%). During treatment with atenolol, two patients had to interrupt their intake of the beta-blocker because of side effects. In the 12 remaining subjects, exercise duration was significantly decreased by 38 +/- 12% (P less than 0.01). Atenolol also induced decreases in plasma-free fatty acid concentration before and after exercise and an increase in potassium concentration after exercise, whereas enalapril and verapamil did not induce metabolic changes. During exercise, systolic blood pressure was decreased by atenolol (P less than 0.001) and enalapril (P less than 0.01) and diastolic blood pressure by enalapril (P less than 0.001), verapamil (P less than 0.05) and atenolol(P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of calcium antagonism on intracellular concentrations and transmembrane fluxes of cations in erythrocytes of men at rest and during exercise.

The effect of calcium (Ca2+) antagonism with felodipine on the intracellular concentrations and transmembrane fluxes of cations in erythrocytes, was studied in 10 normal volunteers at rest and during exercise. All subjects performed two uninterrupted incremental exercise tests on a bicycle ergometer in a randomized order either after placebo administration or after 3 days of pretreatment with felodipine 5 mg t.i.d. Felodipine did not affect the erythrocyte ouabain-sensitive 86rubidium uptake, furosemide-sensitive sodium (Na+)- and potassium (K+)-effluxes and the Na+,Li+-countertransport at rest and during exercise and recovery. Intra-erythrocyte and plasma Na+ and K+ concentrations were not different during felodipine whereas the plasma Ca2+ concentration was significantly increased. Plasma magnesium (Mg2+) concentration was reduced during felodipine treatment while the intra-erythrocyte Mg2+ concentration tended to be increased. The intra-erythrocyte to plasma concentration ratios for Na+ and K+ were not significantly affected by felodipine whereas the ratio for Mg2+ was increased. It is concluded that short-term Ca2+ antagonism with felodipine is not accompanied by major alterations in the intracellular concentrations and transmembrane fluxes of Na+ and K+ in red blood cells of normotensive subjects. The red cell transmembrane gradient for Mg2+ is however altered by felodipine.

Erythrocyte membrane lipids and cationic transport systems in men.

OBJECTIVE: The relationship between erythrocyte membrane and plasma lipids and various transmembrane erythrocyte cationic fluxes was examined in 53 normal men. DESIGN: Different measurements of erythrocyte transport systems were obtained: Na(+)-Li+ countertransport activity; Na+, K+ cotransport activity; Na+, K(+)-ATPase pump activity and the ground membrane permeability for Na+ and K+ as well as the intra-erythrocyte Na+, K+ and Mg2+ concentrations. Plasma cholesterol, triglycerides, phospholipids, free fatty acids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane contents of cholesterol, phospholipids and free fatty acids were obtained from fasting subjects. RESULTS: In single regression analysis the erythrocyte Na(+)-Li+ countertransport and Na+, K+ cotransport activities were negatively related to the erythrocyte membrane cholesterol, phospholipids and free fatty acids contents. The Na+, K(+)-ATPase pump activity as assessed by the ouabain-sensitive Na+ efflux was also inversely related to the membrane cholesterol and phospholipids contents. In multiple regression analysis the red blood cell Na(+)-Li+ countertransport activity was independently and negatively related to the membrane cholesterol and free fatty acids contents. CONCLUSION: Our data show that an elevated level of erythrocyte membrane lipids in normal men is accompanied by lower Na(+)-Li+ countertransport, Na+, K+ cotransport and Na+, K(+)-ATPase pump activities.

Changes in potassium content and membrane potassium channels in circulating cells from normal volunteers treated with cromakalim.

The effect of cromakalim, a K+-channel activator, on the intracellular concentration and transmembrane fluxes of Na+ and K+, was studied in 18 normal male subjects, using a double-blind parallel study design. After a run-in period on placebo for 1 week the subjects were treated with either placebo (n = 6) or cromakalim (n = 12) for 1 week. Blood pressure was not changed during cromakalim administration in these normal male subjects but heart rate was increased. The intraerythrocyte and intraleucocyte K+ concentration was decreased during cromakalim administration while the Ca2+-dependent K+ channels in the red blood cells were increased. No significant effect of cromakalim could be demonstrated on the intracellular Na+ and Mg2+ concentration, on the ouabain-sensitive or bumetanide-sensitive 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+Li+ countertransport, anion carrier and ground membrane leak of Na+ and K+ were also not changed in the cromakalim-treated subjects.

Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems.

BACKGROUND: In order to determine whether alterations in membrane lipids affect transmembrane cationic transport systems in erythrocytes and platelets, cationic fluxes and intracellular cationic concentrations were measured in hypercholesterolaemic patients before and during administration of an inhibitor of 3-hydroxy-3-methlglutaryl coenzyme A reductase. METHODS: After a 1-month run-in placebo period on a lipid-lowering diet the patients were treated, in a double-blind manner, with either placebo (n = 25) or pravastatin (n = 25) for 6 months. Placebo or pravastatin (10 mg during the first month, 20 mg during the second month and 40 mg during the remaining 4 months) was administered once a day in the evening. RESULTS: Compared with the placebo group, the erythrocyte and platelet membrane cholesterol content was reduced in the patients treated with pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was reduced during pravastatin administration, whereas the activity of the erythrocyte and platelet Na(+)-K+ pump was increased. However, the intra-erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and water content, as well as the activities of the erythrocyte Na(+)-Li+ countertransporter and Na+,K+ cotransporter, and Na+ and K+ leakage, were not changed during pravastatin treatment. CONCLUSIONS: The present data show that cholesterol lowering in hypercholesterolaemic patients may result in a significant decrease in erythrocyte and platelet membrane cholesterol content. These changes in membrane cholesterol are accompanied by an increase in activity of the Na(+)-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na+ concentrations.

Correlates of blood pressure in rural and urban Zaïre.

Blood pressure and anthropometric characteristics were studied in 312 rural and 675 urban Bantu of Zaïre aged 10 years and more; proteinuria and the urinary sodium to potassium ratio were determined. On average, systolic and diastolic pressure were higher in rural than in urban Bantu, and rose with advancing age in both populations. However, rural Bantu were older, lighter and smaller, and had a lower sodium:potassium ratio than urban Bantu. Using multiple regression analysis, systolic and diastolic pressures correlated positively with age, weight, pulse rate, sex and sodium:potassium ratio; diastolic pressure also correlated negatively to height. After adjusting blood pressure for these independent correlates, systolic pressure remained significantly higher in rural Bantu. However, no significant difference persisted between the two populations after adjusting blood pressure for age alone. The prevalence of hypertension in rural and urban Bantu increased with age and was 14.2 and 9.9%, respectively, for participants at least 20 years old; women were more affected in the rural area, whereas men were more affected in the urban population. The occurrence of proteinuria was higher in rural Bantu than in urban; it was similar in participants with and without definite hypertension. It is suggested that higher blood pressure in the rural setting was mostly accounted for by the older age of the population.

Salt intake and blood pressure in the general population: a controlled intervention trial in two towns.

A controlled trial was conducted in two Belgian towns to investigate the feasibility and effects of a reduction in salt consumption at the community level. The low-sodium intervention in one town was mainly directed at women and implemented through mass media techniques, while the control town was merely observed. Cross-sectional random sampling at baseline and 5 years later was employed, the participation rate being similar (67%) in the two towns. During the study a total of 2211 subjects were examined. In adult women (greater than or equal to 20 years) in the intervention town the 24-h urinary excretion of sodium (UVNa) decreased by 25 mmol/24 h (P less than 0.001) and this reduction differed (P = 0.01) from the concurrent trend in UVNa in the control town (+8 mmol/24 h). However, both systolic (SBP, -7.5 versus -7.9 mmHg) and diastolic (DBP, -2.3 versus -3.0 mmHg) pressures declined to a similar extent in the women from the two towns. In adult men in the intervention town, decreases were observed in UVNa (-12 mmol/24 h) and in SBP (-5.6 mmHg) and DBP (-2.4 mmHg), but these trends were not significantly different from the concurrent changes in the control town (-14 mmol/24 h, -4.9 and +0.2 mmHg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte and leucocyte sodium and potassium transport systems during long-term diuretic administration in men.

The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The intra-erythrocyte and intra-leucocyte Na+ concentration was increased by 11 and 7%, respectively, during xipamide administration, while the intracellular K+ concentration was decreased by 3 and 4%, respectively. No significant effect of xipamide could however be demonstrated on the ouabain-sensitive, bumetanide-sensitive or ouabain-bumetanide-resistant 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+-Li+ countertransport was also not changed in the xipamide-treated subjects. Our data suggest that the increased intracellular Na+ concentration and the decreased K+ concentration in red and white blood cells of xipamide-treated subjects cannot be attributed to changes in the activity of the Na+ pump, the Na+-K+ cotransport or Na+-Li+ countertransport system or to changes in the number of active Na+ pump units.