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Biomedical subjects

T H Thomas

Publications and source records attributed to T H Thomas.

At least 73 records · Page 4Linked to original sources

Pregnancy induced hypertension and sodium pump function in erythrocytes.

OBJECTIVE: To determine if erythrocyte sodium pump function is altered with the onset of pregnancy induced hypertension. DESIGN: A prospective descriptive study. SUBJECTS: Thirty-two primigravid women with pregnancy-induced hypertension (17 had proteinuria) and 32 gestation-matched normotensive primigravid pregnant women were studied and measurements repeated 20 weeks after delivery. INTERVENTION: Erythrocyte sodium, ouabain-sensitive sodium flux and the sodium pump rate constant were measured in whole blood and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. RESULTS: Blood pressure remained higher after delivery in the women who had been hypertensive during pregnancy. In normal pregnancy erythrocyte sodium was decreased, and ouabain-sensitive sodium flux, the sodium pump rate constant and maximum velocity (Vmax) were increased compared with 20 weeks after delivery. In pregnancy-induced hypertension erythrocyte sodium and sodium pump changes were the same as in normal pregnancy. The possibility of a positive association between changes in erythrocyte sodium and in blood pressure was excluded. The rate constant of the sodium pump in blood was related to its Vmax measured in vitro but the relation had greater variance in the hypertensives with 7 of the 32 women having rate constants greater than expected from their Vmax. CONCLUSION: There was no evidence of sodium pump inhibition or a rise in intracellular sodium associated with increased blood pressure in pregnancy. There may have been stimulation of the sodium pump by a plasma factor in some hypertensive women.

Adult↗

Erythrocyte sodium, potassium and sodium fluxes with cell and subject ageing.

In young subjects erythrocyte sodium was lower in females than in males. In males juvenile erythrocyte sodium decreased with subject age whereas in females aged erythrocyte sodium increased with subject age. Therefore, the difference in erythrocyte sodium between young male and female subjects was not observed in the elderly. These differences in erythrocyte sodium appeared to be mainly due to differences in the sodium pump rate constant. In juvenile cells from young subjects the sodium pump rate constant was related to the ouabain sensitive sodium flux rate, but not in elderly subjects, suggesting disturbed control of cell sodium in the latter group. Juvenile erythrocytes had a higher potassium content in elderly than young subjects but this was mainly in the 'frail' hospitalised elderly and it decreased more rapidly with cell ageing. This could indicate more active erythrocytes entering the blood in elderly subjects and then ageing more rapidly. Differences between young and elderly subjects in erythrocyte sodium, potassium and sodium pump rate constant were more marked in the 'frail' hospitalised elderly.

Adult↗

Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.

Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.

Adult↗

Haemodialysis: effects on white and red blood cell sodium content and transport.

A circulating sodium pump inhibitor, released in response to volume expansion, may, by increasing intracellular sodium concentrations, be responsible for some of the features of the uraemic state. Haemodialysis, by correcting volume overload, would be expected to be associated with a decrease in intracellular sodium towards normal. The effects of a haemodialysis session on leukocyte (WBC) sodium content and transport have not been described and there are conflicting reports of the effects of haemodialysis on erythrocyte (RBC) sodium content and transport. We have measured sodium (NaWBC/RBC) and potassium content (KWBC/RBC), net ouabain-sensitive sodium flux rate (FR) and sodium flux rate constant (RC) before and after a standard haemodialysis session in 20 stable hospital haemodialysis patients. In leukocytes (n = 18), sodium (P = 0.078), FR (P = 0.006), and RC (P = 0.071) decreased over dialysis, whereas in erythrocytes sodium increased (P less than 0.001, n = 19) and RC declined (P = 0.002, n = 18). Although in opposite directions in RBC and WBC, the changes in sodium were toward normal in both cell types. Changes in intracellular sodium content and transport did not correlate with changes in measures of ECF volume or biochemical efficiency of dialysis. We conclude that haemodialysis does affect cell sodium content and transport, but in different ways in different cell types. There was no evidence that haemodialysis removed a sodium pump inhibitor. The use of RBC or WBC as 'model' cells to study sodium transport in uraemia is of questionable validity.

Adult↗

Erythrocyte hydration in normal human pregnancy.

OBJECTIVE: To determine whether the fall in plasma osmolality in normal human pregnancy resulted in cellular overhydration. DESIGN: The changes in erythrocyte hydration, potassium and total osmoles in response to a decrease in osmolality in vitro and associated with the fall in plasma osmolality in normal pregnancy were determined. SUBJECTS: Fifty-one women were studied serially during pregnancy and again 20 weeks after delivery. RESULTS: Erythrocytes from pregnant women exposed in vitro to a 29.9% osmolality decrement had a 28.5% increase in cell hydration. At 14 weeks gestation although plasma osmolality was lower than after delivery (281.1 vs 291.6 mosmol/kg; P less than 0.001) both erythrocyte hydration (1.83 l/kg dry weight cells) and potassium (264 mmol/kg) contents were reduced from the nonpregnant values (1.88 l/kg; P less than 0.01; 272 mmol/kg; P less than 0.001). For the remainder of pregnancy plasma osmolality remained at this lower level but cell hydration and potassium both increased to values at 38 weeks gestation that were greater than in the nonpregnant state (1.92 vs 1.88 l/kg; 287 vs 272 mmol/kg). CONCLUSIONS: These findings suggest that a loss of cell osmoles may be a primary event affecting cell hydration in pregnancy and plasma osmolality is then reduced to maintain normal cell hydration. Subsequent changes in cell hydration were led by changes in intracellular osmole content.

Erythrocytes↗

Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium.

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.

Adult↗

Relationship between the maximum velocity and sodium affinity of the erythrocyte sodium pump and its rate constant in blood.

1. Young and mature erythrocytes from 15 normal subjects were used to compare the sodium pump rate constant measured in whole blood with the more definitive sodium affinity constant and maximum velocity of the sodium pump measured in artificial media using sodium-loaded cells. 2. Similar values were obtained from both erythrocyte fractions for the sodium affinity constant and maximum velocity and also by using two different plots. The median error in the estimate of individual sodium affinity constants and maximum velocities from regression analysis was about 20% and the precision was not improved by combining the data points for the two erythrocyte fractions. 3. The rate constant in whole blood was closely related to the sodium affinity constant and maximum velocity of the sodium pump (r = 0.75), suggesting that it was a reasonable overall assessment of available sodium pump activity. 4. Differences in the rate constant between subjects were due to differences in both the maximum velocity and sodium affinity constant of the sodium pump so that the rate constant could not be used as a guide to the underlying sodium pump physiology.

Adult↗

A serial study of erythrocyte sodium content and sodium pump kinetics in pregnancy.

1. Normotensive primigravid pregnant women were studied longitudinally during pregnancy and 20 weeks after delivery. 2. Erythrocyte sodium content, ouabain-sensitive sodium flux and sodium pump rate constant were measured in whole blood, and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. 3. Erythrocyte sodium content decreased and the sodium pump rate constant increased up to 26 weeks gestation. The increase in rate constant was due to an increase in the affinity of the sodium pump for sodium up to 20 weeks gestation. After 20 weeks gestation there was an increase in maximum velocity and a decrease in sodium affinity of the sodium pump but no further change in the sodium pump rate constant. 4. At 14 weeks gestation the sodium pump rate constant was correlated with both the maximum velocity and sodium affinity constant. After this time the relationship was much more variable and there was no correlation with the sodium affinity constant. The comparison of measurements of the sodium pump in whole blood and in vitro gave no evidence of sodium pump inhibition. 5. The erythrocyte sodium pump changed throughout gestation with different components to the change, but, overall, available sodium pump activity in blood increased and sodium content decreased.

Biological Transport, Active↗

Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension?

Erythrocyte sodium-lithium countertransport was measured in normolipidaemic and hyperlipidaemic hypertensive patients, hyperlipidaemic normotensive patients and normal controls. Hypertension and hyperlipidaemia were each independently associated with raised sodium-lithium countertransport (by analysis of variance, P less than 0.01 and P less than 0.01). The effects were additive so that hyperlipidaemia could not explain raised sodium-lithium countertransport in hypertension. In hyperlipidaemic hypertensive patients, levels of plasma cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were increased, and high-density lipoprotein (HDL) cholesterol was reduced. Of these patients, 73.3% had a known family history of hypertension. Their normotensive first degree relatives were studied, and 48% of these also had raised sodium-lithium countertransport and abnormal plasma lipids (raised cholesterol, triglycerides and LDL cholesterol, and reduced HDL cholesterol). Relatives with normal sodium-lithium countertransport had normal lipids. Therefore, raised sodium-lithium countertransport was associated with the inheritance of both hypertension and hyperlipidaemia, and this could explain why raised sodium-lithium countertransport has been associated with a family history of both hypertension and associated cardiovascular disease.

Antiporters↗

Hypertension and renal dysfunction in primary hyperparathyroidism: effect of parathyroidectomy.

1. Twenty-four patients with primary hyperparathyroidism were studied before and 18 restudied 6.5 months (mean) after parathyroidectomy, to investigate the pathogenesis of the hypertension which may accompany this condition. Comparison was made with age-matched patients with essential hypertension and with normotensive control subjects. 2. There was a significant inverse relationship between mean arterial pressure and 51Cr-labelled ethylene-diaminetetra-acetate (51Cr-EDTA) clearance in patients with hyperparathyroidism both before and after parathyroidectomy, but not in patients with essential hypertension. 3. Creatinine clearance appeared to overestimate glomerular filtration rate in some patients with hyperparathyroidism, falling significantly after surgery while 51Cr-EDTA clearance was unchanged. This observation may explain the failure of some previous studies to relate hypertension to impairment of renal function. 4. Plasma renin activity, plasma aldosterone and whole-body exchangeable sodium did not differ between normotensive and hypertensive patients with primary hyperparathyroidism and were unchanged after surgery. 5. Parathyroidectomy did not result in any change in blood pressure or in glomerular filtration rate measured by 51Cr-EDTA clearance.

Adult↗

Problems in measuring human leucocyte cation content: effects of cell preparation and handling.

1. Previous published measurements of leucocyte cation content are inconsistent, with sodium concentrations having particularly high coefficients of variation. We have measured the effects of recovery time after isolation, different types of handling, and centrifugation on leucocyte sodium and potassium content. 2. Sodium content fell markedly during the first 30 min after isolation and was stable from 1 to 3 h of incubation. There was a small but significant rise in potassium content over the same time period. 3. During incubation, occasional gentle resuspension of the cells gave optimal sodium contents, whereas mixing by inversion caused large falls in sodium and potassium content. 4. Centrifugation of stable cells at 200 g for 6 min caused marked increases in sodium content.

Cell Separation↗

Erythrocyte sodium-lithium countertransport in primary and renal hypertension: relation to family history.

Sodium-lithium countertransport (Na-Li CT) has been reported to be increased in essential hypertension (EHT) but the nature and degree of distinction from normal controls in unclear. Of 44 unselected patients with EHT in the hospital hypertension clinic 36% had Na-Li CT greater than the normal control range and 70% of these had a family history of hypertension. Almost all the patients with normal Na-Li CT had no family history of hypertension. Analysis of variance showed that raised Na-Li CT was related to both a family history of hypertension and a family history of a cardiovascular event. Of 23 patients with hypertension secondary to renal disease, 43% had Na-Li CT greater than the normal control range and raised Na-Li CT was related to both a family history of hypertension and a family history of cardiovascular event in the same way as EHT. Raised Na-Li CT was not characteristic of EHT but identified a subgroup of patients with EHT and a family history of hypertension, some of whom also had renal disease.

Adult↗

Erythrocyte sodium and sodium flux in relation to hypertension in chronic renal failure.

Erythrocyte sodium and sodium fluxes in plasma and in physiological buffer solution were studied in normotensive and hypertensive uraemic patients and normal subjects. Erythrocyte sodium was reduced in the uraemic patients due primarily to low sodium influx, further supported by low passive membrane permeability. These differences were much more marked in normotensive patients. There was no evidence for sodium pump inhibition in the erythrocytes. The low erythrocyte sodium influx in the uraemic patients appeared to be due to a plasma factor which could be reversed in young cells but not in old. However, erythrocyte sodium flux in both plasma and physiological buffer was lower in normotensive than in hypertensive uraemic patients. Therefore, a membrane change to compensate for the effects of the plasma factor on sodium influx may be related to the development of hypertension in the uraemic patients.

Adult↗

Hypertension and hyperinsulinaemia: a relation in diabetes but not essential hypertension.

To investigate the hypothesis that insulin resistance is concerned in the pathogenesis of essential hypertension fasting glucose/insulin and fasting insulin/C-peptide ratios were measured in non-obese normotensive and hypertensive diabetic and non-diabetic subjects. Patients with essential hypertension had normal fasting serum insulin values and normal fasting glucose/insulin ratios; by contrast, the hypertensive non-insulin-dependent diabetic subjects had higher fasting serum insulin and lower glucose/insulin ratios than either normotensive diabetic or non-diabetic patients. Both hypertensive and normotensive diabetic subjects had higher fasting C-peptide values than those without diabetes. Hypertensive diabetic patients had the highest insulin/C-peptide ratios, indicating low hepatic insulin extraction rates. These findings suggest that hyperinsulinaemia is not causally related to essential hypertension but that it may contribute to the hypertension of non-insulin-dependent diabetes in association with low hepatic insulin clearance.

Analysis of Variance↗