Variations in the apparent pH set point for activation of platelet Na-H antiport

To explore the role of the Na-H antiport in essential hypertension, we studied the kinetics of cytosolic pH and external sodium activation of this transport system in platelets from 65 normotensive and essential hypertensive subjects on and off antihypertensive medications. Subjects included both blacks and whites, as well as men and women. The fluorescent dye 2′7-bis(carboxyethyl)-5,6-carboxyfluorescein was used to monitor the cytosolic pH in these cells. Platelets from black (hypertensive and normotensive) men and hypertensive white men demonstrated a highly significant alkaline shift in the apparent cytosolic pH set point for activation of the Na-H antiport. For the hypertensive subgroups, the cytosolic pH set point values (mean±SEM) were: white men, 7.45±0.052; white women, 7.04±0.089; black men, 7.66±0.148; and black women, 7.20±0.082. For the normotensive subgroups, the cytosolic pH set point values were: white men, 7.13±0.034; white women, 7.05±0.036; black men, 7.50±0.110; and black women, 7.20±0.176 (p=0.0016 for race and p=0.0001 for gender, using a three-way analysis of variance by race, gender, and hypertension). There were no race-, gender-, or blood pressure-related differences among the various cohorts in the kinetics of sodium activation of the Na-H antiport, the cellular buffering power, and basal pH. These results suggest that at basal pH the Na-H antiport is quiescent in platelets from both black and white women and normotensive white men. However, it can be active at basal pH in platelets from black men (normotensive and hypertensive) and in platelets from hypertensive white men. Our work demonstrates the heterogenous nature of the alterations in the Na-H antiport in essential hypertension and its dependence on gender and racial extraction.