KINETIC ABNORMALITIES OF THE RED-BLOOD-CELL SODIUM-PROTON EXCHANGE IN HYPERTENSIVE PATIENTS

The present study was designed to examine the kinetics of Na+-H+ exchange in red blood cells of normotensive and hypertensive subjects and its relation to the previously reported abnormalities in Na+-Li+ exchange. The Na+-H+ antiporter activation kinetics were studied by varying cell pH and measuring net Na+ influx (mmol/l cell x hr = units) driven by an outward H+ gradient. The Na+-Li+ exchange was determined at pH 7.4 as sodium-stimulated Li+ efflux. Untreated hypertensive patients (n = 30) had a higher maximal rate of Na+-Li+ exchange (0.43 +/- 0.05 versus 0.26 +/- 0.02 units, p < 0.0003), a higher maximal rate of Na+-H+ exchange (62.3 +/- 6.2 versus 47 +/- 4 units; p < 0.02), but a similar affinity for cell pH compared with normotensive subjects (n = 46). The cell pH activation of the Na+-H+ antiporter exhibited a lower Hill coefficient than that of normotensive subjects (1.61 +/- 0.12 versus 2.56 +/- 0.14; p < 0.0001). This index of occupancy of internal H+ regulatory sites was found reduced in most of the hypertensive patients (73%) whether their hypertension was untreated or treated. Hypertensive patients with Na+-Li+ exchange above 0.35 units (0.68 +/- 0.057 units, n = 16) did not exhibit elevated maximal rates of Na+-H+ exchange (57.3 +/- 10 units, NS) in comparison with those with Na+-Li+ exchange below 0.35 units (66.4 +/- 7.6 units, n = 26), but both groups exhibited reduced Hill coefficients. Hypertensive patients with enhanced Na+-H+ exchange activity (more than 90 units) had normal maximal rates of Na+-Li+ exchange. We propose that the elevated maximal rate of Na+-Li+ exchange and the low Hill coefficient for Na+-H+ exchange activation seen in many hypertensive patients might reflect a higher number of antiporter sites or abnormal antiporter regulation by phosphorylation.