Countertransport In Erythrocytes Research Articles

Insulin sensitivity, sodium-lithium countertransport and platelet free calcium concentrations in normotensive men with a family history of hypertension.

Peripheral glucose disposal (assessed with the euglycaemic-hyperinsulinaemic clamp technique), Na+-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 36 men from families with essential hypertension in at least two close relatives and in 28 age- and weight-matched men from families without hypertension. All had diastolic blood pressure consistently below 90 mm Hg and a normal oral glucose tolerance test. The mean age of the study population as a whole was 37 years (range 24-46). Insulin sensitivity index values (glucose disposal/serum insulin concentration during the clamp) were lower in the familial hypertension group than in the control group, but the two groups did not differ in Na+-Li+-countertransport, or in the platelet cytosolic free Ca2+ concentration which was correlated to the waist: hip circumference ratio in both groups (r = 0.38 and r = 0.49, respectively). The present findings do not support the hypothesis that an increase in Na+-Li+ countertransport activity or the platelet cytosolic free Ca2+ concentration is a marker of insulin resistance in hypertension prone men.

Some peculiarities of personal profile and morphovegetative constituthion in healthy people at different level of na+/li+ countertransport in erythrocyte membranes

Personal characteristics in combination of vegetative homeostasis were studied, and also type of morphoconstitution in association with one of genetic marker - velocity of Na+/ Li+ countertransport in erythrocyte membranes of 192 healthy people, aged from 17 to 42 y.o. Trends to increase the anxiety level in patients of both sex in all age groupes were determined at the velocity range of Na + /Li+ countertransport in erythrocytes: from 162 to 278 mс Mol Li/1 c h, which were most expressed in asthenic morphoconstitution people with sympathicotonic type of vegetative effects, this being combined with disadaptive forms of vegetative reactions.

A pilot study of erythrocyte lithium-sodium countertransport in women during the menstrual cycle.

The study investigated lithium-sodium countertransport in erythrocytes of normal female volunteers during different phases of the menstrual cycle or during administration of oral contraceptives. Ten normally menstruating, and eight oral contraceptive using, normal female subjects were studied over at least one cycle. Erythrocyte lithium-sodium countertransport was determined using. standard, previously validated methods at different phases of the menstrual cycle. Hematological, electrolyte, blood pressure and other transport measures were also made and these were related to the self-reported incidence of premenstrual symptomatology. A correlation, (p < 0.02), was found between lithium-sodium countertransport rate and the premenstrual symptom severity score but only in the premenstrual phase. There was no correlation between any of the electrolyte, blood pressure or hematological data and lithium-sodium countertransport rate nor between it and other ion transport measures. Pre-menstrual symptomatology was conspicuously absent from those subjects taking oral contraceptives. Cyclical fluctuations in normally menstruating women, and differences between them and oral contraceptive users, were seen in lithium-sodium countertransport rate although the groups were too small to show statistical significance. Care was taken to exclude influences due to circadian, dietary and diurnal variations and the present results show somewhat less within-individual variability in erythrocyte lithium-sodium countertransport during the menstrual cycle than do other reports in the literature. Some interesting features were observed which justify a much larger scale study than the present pilot experiment which should involve a larger number of subjects studied over more than one cycle and in particular a more detailed study of the ovulatory phase.

Sodium-lithium countertransport and platelet cytosolic free calcium concentration in relation to peripheral insulin sensitivity in postmenopausal women.

1. Peripheral glucose disposal (assessed by the euglycaemic-hyperinsulinaemic clamp technique), Na(+)-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 41 women with impaired glucose tolerance and in 38 women with normal glucose tolerance. The groups were matched for body mass index (range 18-44 kg/m2) and diastolic blood pressure (range 58-109 mmHg). 2. Na(+)-Li+ countertransport was correlated significantly with body mass index, basal plasma insulin concentration and basal plasma glucose concentration, and was inversely correlated with peripheral glucose disposal rate. Stepwise regression analysis showed that Na(+)-Li+ countertransport was positively correlated with basal plasma insulin concentration (r2 = 8.7%). 3. Systolic blood pressure was correlated with fasting plasma insulin concentration (model r2 = 25%) and with Na(+)-Li+ countertransport (model r2 = 34%) in the group with impaired glucose tolerance. In the group with normal glucose tolerance there were no correlations between blood pressure and Na(+)-Li+ countertransport. 4. No correlation was found between platelet cytosolic free Ca2+ concentration and any of the variables measured. 5. It is concluded that Na(+)-Li+ countertransport is correlated with the degree of peripheral insulin sensitivity and with the plasma insulin concentration. Platelet cytosolic free Ca2+ concentration was not correlated with any of these variables, and there was no relationship between Na(+)-Li+ countertransport and the platelet cytosolic free Ca2+ concentration.

Vascular responsiveness and cation exchange in insulin-dependent diabetes.

1. We measured forearm blood flow during brachial artery infusions of vasoconstrictors (angiotensin II and noradrenaline) and vasodilators (sodium nitroprusside and carbachol) in 16 healthy control subjects and in 18 patients with uncomplicated insulin-dependent diabetes mellitus. Erythrocyte Na+/Li+ countertransport and platelet Na+/H+ antiport activities were also measured. 2. The mean basal forearm vascular resistance was 22% lower in diabetic patients than in control subjects. The effects of each infusion on forearm vascular resistance were similar in diabetic patients and control subjects. 3. Erythrocyte Na+/Li+ countertransport activities were similar in diabetic patients and control subjects. Platelet Na+/H+ exchange (Vmax) was approximately 40% greater in diabetic patients than in control subjects, whereas the Km for Na+ was similar. 4. In diabetic patients, but not in control subjects, the responses to sodium nitroprusside and carbachol correlated inversely with Na+/Li+ countertransport in erythrocytes (rs = -0.76, P less than 0.001, and rs = -0.66, P less than 0.005, respectively), but not with Na+/H+ exchange in platelets.

Reduction of Li(+)-Na+ countertransport by physiological levels of insulin in vitro.

We studied the effect of insulin at concentrations of 0 to 50 mU/l and glucose at 0 to 20 mmol/l on Li(+)-Na+ countertransport in erythrocytes from normotensive human subjects. While insulin produced a dose-dependent decrease in the rate of Li(+)-Na+ countertransport, from 0.272 mmol/l erythrocytes per h at zero insulin to 0.081 at a concentration of 50 mU/l (P less than 0.0001), alterations in ambient glucose concentration had no significant effect on the rate of countertransport. Physiological levels of insulin appear to reduce Li(+)-Na+ countertransport in vitro by a mechanism which is not related to glucose concentration or transport.

Erythrocyte Na,Li Countertransport and Arterial Pressure in Diabetic Adolescents

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

Increase in Glomerular Filtration Rate in Patients with Insulin-Dependent Diabetes and Elevated Erythrocyte Sodium–Lithium Countertransport

Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.

Na+-H+ exchange and other ion-transport systems in erythrocytes of essential hypertensives and spontaneously hypertensive rats: a comparative analysis

The activity of ion-transport systems and Ca2+-induced erythrocyte haemolysis were compared between patients with essential hypertension and two strains of spontaneously hypertensive rats. Previous data on the increased rate of Na+-Li+ countertransport in erythrocytes of essential hypertensives were confirmed in this study. However, identification of Na+-Li+ countertransport in rat erythrocytes remained a complicated person because of the high rate of sodium-independent efflux of Li+. The rate of Na+-H+ exchange increased by 50-80% both in spontaneously hypertensive Wistar-Kyoto rats (SHR) and in patients with essential hypertension. No difference between Milan hypertensive strain rats (MHS) and Milan normotensive strain rats (MNS) was found. The rate of Na+,K+ cotransport increased in SHR and MHS erythrocytes compared with rats of the control strains [normotensive Wistar-Kyoto rats (WKY) and MNS; 30-50 and 90-110%, respectively]. No difference in this parameter was found between patients with essential hypertension and healthy subjects. Erythrocytes of patients with essential hypertension and of SHR were characterized by a higher sensitivity of their K+ channels to the increased concentration of intracellular Ca2+. This parameter did not change in MHS erythrocytes. Ca2+-induced haemolysis increased four- to fivefold in MHS erythrocytes compared with MNS and did not change in erythrocytes of SHR and patients with essential hypertension. The conclusion from these data is that the SHR strain is a more adequate model of human essential hypertension than the MHS.

Red-cell sodium-lithium countertransport and fractional excretion of lithium in normal and hypertensive humans.

To examine the relations between erythrocyte sodium-lithium countertransport and renal proximal tubular sodium handling, we measured countertransport, and then subjected 30 normal and 32 hypertensive subjects, both white and black, to provocative maneuvers of volume expansion and contraction. The fractional excretions of sodium and lithium were measured simultaneously. In agreement with previous studies, we found that countertransport in erythrocytes was elevated in hypertensive patients compared with normal subjects. We also observed that whites have a higher level of countertransport than blacks. In the basal state, we found that fractional sodium excretion of hypertensive patients was no different than in normal subjects, whereas the fractional lithium excretion of hypertensive persons was increased compared with normotensive values. Volume expansion with 2 1 0.9% saline administered intravenously during a 4-hour period provoked an exaggerated natriuresis and a greater increase in fractional lithium clearance in hypertensive patients compared with the control group. With volume expansion and contraction, fractional lithium clearance and countertransport were directly correlated. Our data suggest that hypertensive persons do not have increased proximal tubular sodium reabsorption compared with normal subjects. Further, the exaggerated natriuresis of hypertension is, in part, the result of increased distal solute delivery. The fact that our hypertensive patients were older may partially explain the discrepancies between this report and previous observations.

Elevated intracellular Ca 2+ affects Li i-Na o countertransport in human red blood cells

Changes in cytoplasmic Ca 2+ concentration and in Li i-Na o countertransport activity have been shown to be associated with essential hypertension. Elevated intracellular free [Ca 2+], as well as abnormalities of Ca 2+ binding and transport have been reported in cells from different tissues of hypertensive laboratory animals and essential hypertensive patients. Similarly, enhanced rates of Li i-Na o countertransport and the modified pattern of the temperature dependence of this activity in red blood cells from essential hypertensive patients have been previously demonstrated. The aim of the present study was to investigate possible interaction between changes in intracellular free [Ca 2+] and the Li i-Na o exchange in human red blood cells. The ionophore ionomycin was used to allow Ca 2+ incorporation into the cells in a dose-dependent manner. The elevation of intracellular [Ca 2+], in turn, resulted in enhanced Li + efflux from the cells. At 3 μM, ionomycin selectively and significantly enhanced the Li i-Na o countertransport but not Li + leakage from the cells. EGTA totally abolished the effect of ionomycin, indicating that the effect is directly related to Ca 2+. As low as 0.4 μM Ca 2+ caused a statistically significant effect. The maximal effect of Ca 2+ on the Li i-Na o countertransport was achieved around the external pH range of 6.8–7.5. In contrast, the leakage of Li + was significantly enhanced by Ca 2+ at a pH of 7.4 and above. Ca 2+ did not affect the K m of the Li i-Na o countertransport for Li +. Amiloride, which inhibits Na + H + exchange, inhibited only 10% of the Ca 2+-enhanced countertransport. It is concluded that Ca 2+ may play a role in the regulation of Li i-Na o countertransport in erythrocytes.

Membrane polyunsaturated fatty acids and lithium-sodium countertransport in human erythrocytes

Two groups of individuals, 26 normotensive normolipemic and 37 normotensive hyperlipemic, all without family hystory of hypertension have been selected in attempt to demonstrate whether LiNa countertransport of erythrocytes is influenced by plasma and membrane lipid composition. The maximal rate of LiNa countertransport was elevated in hyperlipemics (0.344±0.168 vs 0.220±0.074 mmol/l erythrocytes/h). This difference is highly significant. Hyperlipemics had different composition of membrane lipids than normals. The most important variations were: increase of palmitic, palmitoleic and total saturated fatty acids (SFA) as well as increase of cholesterol/phospholipids ratio (C/PL); in contrast, hyperlipemics had a reduced amount of linoleic acid and total unsaturated fatty acids (UFA) as well as total polyunsaturated fatty acids (PUFA). Consequently, UFA/SFA and PUFA/SFA ratios were lower than in normals. LiNa countertransport was negatively correlated with the amount of PUFA (p<0.02), whereas it was positively correlated with the following parameters: oleic/linoleic ratio (p <0.02), monounsaturated fatty acids/polyunsaturated fatty acids ratio (p <0.03) as well as with the SFA+monounsaturated fatty acid/PUFA ratio (p <0.03). These findings suggest that the V max of LiNa countertransport in erythrocytes is influenced by the lipid composition of the membrane.

Lithium ion transport by erythrocytes of randomly selected blood donors and manic-depressive patients: lack of association with affective illness

The authors measured the in vitro lithium ion ratio and maximal rate of sodium-lithium countertransport in erythrocytes of 739 randomly selected blood donors and 42 manic-depressive patients to determine the frequency distributions of these two variables in a general population and their relationship to one another and to affective illness. A large interindividual variation was found for the ratio and countertransport, and there was evidence of bimodality in the frequency distributions for these two traits. There was a moderate negative correlation (r = -.61) between the ratio and countertransport for 126 individuals. Neither the ratio nor countertransport was found to be a useful marker for affective illness.

Sodium-lithium countertransport in erythrocytes of children and adolescents with hypertension.

We have investigated the sodium-lithium countertransport system as a screening test for hypertensive disease in children and adolescents using the method of Canessa et al. [New Engl. J. Med. 302: 772-776, 1980]. The sodium-lithium countertransport in erythrocytes was measured in patients, ages 4-18 years, having essential hypertension or secondary hypertension and compared with age-, weight-, sex- and race-matched normotensive controls. Children and adolescents with essential hypertension possessed a significantly higher erythrocyte sodium-lithium countertransport rate than the normotensive control group (0.39 +/- 0.18, n = 28, vs. 0.22 +/- 0.14 mmol Li/l red cells/h, n = 20, respectively; p less than 0.001). Children with secondary hypertension had intermediate values (0.31 +/- 0.15 mmol Li/l red cells/h; n = 17) which did not differ significantly from values of subjects with essential hypertension or normotensive controls. There was no correlation of counter-transport values with age, sex, or body weight in either hypertensive or normotensive groups. However, white normotensive children had significantly higher countertransport levels compared with black normotensives (0.32 +/- 0.14, n = 10, vs. 0.13 +/- 0.07 mmol Li/l red cells/h, n = 10, respectively; p less than 0.005). Similarly, white children and adolescents with essential hypertension had higher mean countertransport measurements than did black hypertensives (0.42 +/- 0.20, n = 21, vs. 0.27 +/- 0.05 mmol Li/l red cells/h, n = 7, respectively) although this difference did not reach statistical significance (p less than 0.1). Although children and adolescents with essential hypertension had a significant elevation of sodium-lithium countertransport when compared to normotensives, the large degree of overlap of countertransport values in these two groups, as well as the intermediate values of children with secondary hypertension, limits the usefulness of the sodium-lithium countertransport as a screening test for essential hypertension in this population. Taking into account the influence of racial differences on the countertransport assay does not sufficiently improve the discriminatory value of the test to render it clinically useful.

Hemodialysis does not affect erythrocyte sodium-lithium countertransport

Sodium-lithium countertransport measurements on erythrocytes are currently of interest because some hypertensive subjects and their relatives have abnormally high values. Woods et al [1] reported that red cells taken from dialysis patients after hemodialysis had significantly lower sodium-lithium countertransport than before dialysis. They suggested that sodium-lithium countertransport is influenced by ‘a dialyzable plasma factor’. We conducted experiments to further evaluate their observations relating to the ‘dialyzable plasma factor’. However, we have been unable to confirm their findings. Neither an effect of hemodialysis on sodium-lithium countertransport in erythrocytes from maintenance dialysis patients nor any effect of dialysis on normal erythrocytes in vitro was evident. Our results do not support the existence of a dialyzable plasma factor affecting sodium-lithium countertransport.

The antihypertensive effect of calorie restriction in obese adolescents: dissociation of effects on erythrocyte countertransport and cotransport.

Measures of maximal rates of lithium-sodium countertransport and frusemide-sensitive sodium and potassium cotransport have been proposed as biochemical markers for human essential hypertension. The stability of these functions over time within the same individuals has led to the suggestion that maximal transport capacities are genetically determined. The present study confirms the reproducibility of functional assays of countertransport and cotransport in human erythrocytes after overnight storage and over a six-month period in normal volunteers and provides estimates of the magnitude of technical error for each assay. A long-term dietary intervention study in a group of obese adolescents demonstrated marked increases in erythrocyte sodium levels and maximal frusemide-sensitive sodium and potassium fluxes but no changes in cell potassium or water and no effect on lithium-sodium countertransport. A correlation between the decrease in percentage of body fat and the increase in cell sodium content suggests a link between the metabolic effects of dieting and control of erythrocyte cation handling. Although the mechanism linking dietary calorie restriction and changes in erythrocyte cation metabolism is unknown, evaluation of body weight, and especially recent weight loss, is important in studies of erythrocyte transport. Conclusions regarding genetic contributions to the activities of lithium-sodium countertransport and sodium-potassium cotransport systems will be strengthened by clarification of environmental regulators.

The erythrocyte membrane in essential hypertension characterization of the temperature dependence of lithium efflux

Erythrocytes of most patients with essential hypertension are distinguished by a typical pattern of temperature-dependence of Li efflux. In the present study we have attempted to characterize this unique temperature response. Measurements of Li efflux into Na medium and Li i-Na o countertransport were conducted simultaneously at finely spaced temperature intervals with increments of 1 to 2°C in the range of 10–40°C. The Arrhenius plots for the efflux in Na medium and for Li i-Na o countertransport in erythrocytes of both normotensives and hypertensives were biphasic with slopes representing apparent energies of activation of about 28 and 8 kcal/mol below and above the ‘break’, respectively. However, the ‘break’ in the Arrhenius plot appeared at distinctly different temperatures: 30°C for normotensives and 20°C for hypertensives. The Li efflux was resolved into N-ethylmaleimide-sensitive and -insensitive components. The sensitive component exhibited a typical biphasic temperature response, with the characteristic ‘break’: at 30°C for normotensives and at 20°C for hypertensives. In contrast, the N-ethylmaleimide-insensitive component was alike in normotensives and hypertensives. It is concluded that: (a) the unique temperature dependence of Li efflux in erythrocytes of hypertensives results from a localized modification in the membrane; (b) the N-ethylmaleimide-sensitive component represents a protein moiety which distinguishes between the erythrocyte membrane of normotensives and hypertensives; (c) the expression of the temperature dependence as judged by the sharp transition in slope (within 1 to 2°C), apparently reflects the cooperative involvement of membrane lipids, associated with the Li efflux system.

Sodium-lithium countertransport in erythrocytes of hypertension prone families in Utah.

Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.

Lithium-sodium countertransport in erythrocytes of normal and hypertensive subjects. Relationship with age and plasma renin activity.

Lii-Nao countertransport was measured in red blood cells of 58 normotensive subjects (27 females and 31 males), 60 patients with essential hypertension (26 females and 34 males), and in 28 with secondary hypertension (19 females and 9 males). The mean values (+/- SEM) expressed as mmol Li (1 red cells X hr)-1 were 0.18 +/- 0.02 (females) and 0.20 +/- 0.01 (males) in the control group, 0.34 +/- 0.04 (females) and 0.39 +/- 0.03 (males) in essential hypertension, 0.16 +/- 0.03 (females) and 0.19 +/- 0.02 (males) in secondary hypertension. The mean value of Lii-Nao countertransport obtained in essential hypertension was statistically different from those obtained in both normals (p less than 0.001) and patients with secondary hypertension (p less than 0.001). A negative correlation was found between age and Lii-Nao countertransport in normotensive males (r = - 0.648; p less than 0.001) but neither in normal females nor in patients with essential hypertension. A positive correlation (r = + 0.425; p less than 0.05) was found between plasma renin activity after intravenous furosemide and Lii-Nao countertransport in essential hypertension. These findings support the hypothesis of a characteristic cation transport across the red blood cell membrane of patient with essential hypertension which might be correlated with the plasma renin activity.

Increased Sodium-Lithium Countertransport in Erythrocytes of Pregnant Women

TWO groups of investigators1 , 2 have shown that erythrocyte sodium–lithium countertransport is higher in patients with essential hypertension than in normotensive subjects. These observations prompted us to investigate sodium–lithium countertransport in normal and hypertensive pregnant women to ascertain whether the relation between cation flux in these two groups of subjects was similar to the observed difference between normal and hypertensive nonpregnant women. We reasoned that if countertransport in women with ppregnancy-induced hypertension differed from that in normal pregnant women, prospective measurement of cation flux during pregnancy might lead to a useful technique of identifying incipient ppregnancy-induced hypertension. Differences in counter-transport between . . .