Leucocyte intracellular pH and Na+ -H + exchange activity in essential hypertension: an in vitro study under physiological conditions


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Abstract

The cellular basis for essential hypertension remains obscure. Abnormal ion transport has been demonstrated in both experimental and essential hypertension, raised levels of sodium—lithium (Na+-Li + ) and sodium-proton (Na+-H + ) exchange in blood cells being a consistent feature. However, Na+—H+ exchange is not the main regulator of intracellular pH at resting pH, while the importance of the contribution of bicarbonate to cellular pH regulation is now increasingly appreciated. Serum and serum-derived growth factors are known to affect intracellular pH and the activity of the Na+—H + antiporter. This study was designed to investigate the activity of Na+—H+ exchange in the leucocytes of patients with essential hypertension in the presence of bicarbonate in vitro and to measure the effect of autologous serum on intracellular pH and Na+—H+ exchange. Paired serum samples from essential hypertensives and their controls were used on leucocytes from other (unrelated, normotensive) donors to investigate the same parameters. In a study of 30 patients with untreated essential hypertension and 30 controls matched for age, sex, race and body habitus we found no difference in resting pH or buffering capacity (pH 7.28 ± 0.01 and 32.0 ± 1.6mmol/l per pH, hypertensives, versus 7.27 ± 0.02 and 34.5 ± 1.8mmol/l per pH, controls), but a marked difference in the maximal rate of Na+-H + exchange in response to intracellular acidification (57.8 ± 3.2 mmol/l per min versus 47.2 ± 1.4 mmol/l per min, P=0.004). Serum from both hypertensives and controls caused an intracellular alkalinization in their own cells, brought about by stimulation of Na+-H+ exchange (pH 7.39 ± 0.02, hypertensives, compared with 7.38 ± 0.02, controls). No difference was seen, however, in intracellular pH, in buffering power or in activity of Na+-H+ exchange between leucocytes from third-donors incubated with either serum from hypertensives or controls (pH7.39 ± 0.03, 30.1 ± 1.9 mmol/l per pH and 54.1 ± 1.7 mmol/l per min, serum from hypertensives, versus 7.36 ± 0.04, 31.5 ± 2.0 mmol/l per pH and 51.8 ± 1.5 mmol/l per min, serum from controls, n=20). In the hypertensive group, serum cholesterol was negatively correlated with leucocyte intracellular pH and triglyceride positively correlated with proton efflux rate. Diastolic blood pressure correlated with proton efflux rate for the hypertensives, but not for the controls. These findings indicate that the increase in proton efflux rate seen in the hypertensive group may play a role in the pathophysiology of hypertension and suggest that changes in the cell membrane, via alterations in lipid content, affect the activity of the N a + - H + transport system.

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