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

Abstract

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 antlhypertensive 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/>=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. (Hypertension 1990;16:180-189) T he current consensus holds that alterations in the cellular regulation of cytosolic free calcium (Caj) and cytosolic sodium (Naj) participate in the pathophysiology of essential hypertension. This concept has emerged from numerous studies demonstrating that several ion transport systems are altered in this disease. Recently, the focus of a number of investigations has been on human platelets, inasmuch as these circulating cells are responsive to a variety of agonists that regulate Caj and Naj. Moreover, platelets share characteristics with vascular smooth muscle cells, which play an important role in the increased peripheral vascular resistance that occurs in essential hypertension. One

Sodium Bicarbonate Cotransporter Polymorphisms Are Associated With Baseline and 10-Year Follow-Up Blood Pressures

“…In this case, intracellular pH could be affected. Na-Li CNT is activated as cellular pH decreases 12 and could show compensatory activity. Although Na-Li CNT essentially is a Na-Na transporter in vivo, it has been thought by some to function as a Na-H antiporter in the presence of increased intracellular acidity, particularly in the proximal tubules of the kidney.…”

Renal acid excretion and intracellular pH in salt-sensitive genetic hypertension.

“…In this respect we wish to note that in platelets and in cultured vascular smooth muscle cells from hypertensive models overactivity of the Na+/H' antiporter has been described in association with a normal (35) or a high pHi (36). These seemingly contradictory findings can be explained, in our opinion, on the basis of in vitro platelet hyperreactivity which has been described in platelets from hypertensive subjects (37) or stimulation of the antiporter during enhanced growth in culture, a feature of vascular smooth muscle cells from the SHR (36,38).…”

Effects of angiotensin II and endothelin-1 on platelet aggregation and cytosolic pH and free Ca2+ concentrations in essential hypertension.

“…4 Intracellular pH (pH,), which is partially regulated by the Na + -H + exchanger, also controls vital cellular functions 5 and provides a metabolic milieu in…”