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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

The cationic fluorescent probe, DiSC,(5) was used to measure the membrane potential in human platelets. Hyperpolarization was induced by the addition of Ca2+ to the medium and also by the addition of the Ca2+ ionophore, A23187. In the absence of extracellular Ca2+ ([Ca'+],) there was no response to A23187. The threshold concentration for [Ca2+]., was 20 fiM and for A23187 was 12 nM. The increase polarity induced by [Ca2+lO was not affected by various K' channel blockers. However, the effect of A23187 was inhibited by quinine and charybdotoxin, while apamin, tetraethylammonium, and the calmodulin inhibitors trifluoperarine and compound I324571 were ineffective. The resting membrane potential was -66 f 0.9 mV and was decreased by quinine. There are three conclusions from this study: (i) Ca2+-activated K+ channels exist in human platelets: (ii) they are the type that are apamin insensitive, charybdotoxin sensitive; and (iii) they may contribute to the resting membrane potential. [P.S.E.B.M. 1989[P.S.E.B.M. , VoI 1921 nimal cell plasma membranes possess K+ channels, which, when opened, induce cytoplasmic

Objective.\p=m-\Toinvestigate the patterns of electrolyte abnormalities resulting from thiazide administration and whether they cause ventricular arrhythmias, and to help resolve the controversy over whether clinicians should routinely prescribe potassium-conserving therapy to all patients treated with thiazides.Design.

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