M.T. Aguilera

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)

Abnormal Na+-K+ ATPase kinetics in a subset of essential hypertensive patients

Abstract 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.

Comparative evaluation of the antihypertensive efficacy of once-daily amlodipine versus nitrendipine with 24-hour ambulatory blood pressure monitoring in essential hypertension.

Summary We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 ± 14/102.5 ± 6 vs. 167.1 ± 14/98.7 ± 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, −22.3 ± 13 vs. −19.1 ± 16 mm Hg) and diastolic BP (DBP, −12.0 ± 5 vs. −8.1 ±8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 ± 10 vs. 132.5 ± 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 ± 6 vs. −5.2 ± 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 ± 4 vs. −3.7 ± 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.

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

SummaryWe 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 µmol.(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.