Kinetics of the human leucocyte Na(+)-H+ antiport in essential hypertension.
Many membrane abnormalities have been described in human essential hypertension that may lead to an increased intracellular Na+ content, an example being reduced Na+ efflux by the sodium pump. We have previously found increased Na(+)-H+ antiport activity in leucocytes of hypertensive subjects. In the present study we examined the kinetics of this pump in 16 hypertensive and 20 carefully matched normotensive subjects by loading cells to different intracellular pH levels (as measured by fluorimetry) using a double-ionophore technique. The maximal rate of ethyl isopropyl amiloride-sensitive H+ efflux was significantly raised in leucocytes from the hypertensive subjects [75.3 +/- 6.2 versus 48.8 +/- 2.1 mmol/l per min in normotensives (mean +/- s.e.m.); P less than 0.001]. There was no difference in the affinity of the Na(+)-H+ antiport for intracellular H+. Intracellular buffering power at different internal pH levels in the range 6.0-7.1 did not differ in the two groups. We conclude that one reason for the reported intracellular alkalinity and increased sodium content of leucocytes from hypertensive subjects in bicarbonate-free media could be an increased number of active Na(+)-H+ exchangers or an increased turnover rate for each exchanger. A similar defect in vascular smooth muscle could account for the increased tone and thickening of the media. The abnormal maximal transport capacity of the leucocyte may be a useful membrane marker for future studies in human hypertension.
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Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Fennell
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Dudley
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D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D015222:Sodium Channels / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers