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Several reports indicate that erythrocytes (RBCs) from blacks and men have higher sodium concentrations than those from whites and women. One possible mechanism to explain this finding is a difference in the activity of Na'-K+-ATPase. To explore this possibility, we have studied the Na' And K+ kinetics of RBC Na'-K+-ATPase and RBC Na' and KV concentrations in 37 normotensive blacks and whites, both males and females. The maximal initial reaction velocity (V..,[) values for RBC Na'-K+-ATPase were lower in blacks and men as compared with whites and women. Higher RBC Na+ levels were observed in blacks and males vs. whites and females. Significant inverse correlations were noted between the Na+-K+-ATPase activity and RBC Na+ concentrations. These findings indicate that cellular Na+ homeostasis is different in blacks and men as compared with whites and women. Since higher RBC Na+ concentrations have also been observed in patients with essential hypertension as compared with normotensive subjects, the higher intracellular Na' concentrations in blacks and men may contribute to the greater predisposition of these groups to essential hypertension.

In this work, we explored the role of cyclic nucleotides in modulating parameters of the Na/H antiport in human platelets. Sodium nitroprusside and iloprost, as well as cyclic nucleotide analogues, were used to raise cellular levels of cAMP and cGMP. Cyclic nucleotides reversed the thrombin-evoked alkaline shift in cytosolic pH set point and the activity of the Na/H antiport, concurrently with attenuation of thrombin-induced rise in cytosolic free Ca. No effect of cyclic nucleotides was observed in platelets not treated with thrombin, or platelets subjected to phorbol 12-myristate 13-acetate. cAMP did not reverse ionomycin-induced changes in the parameters of the Na/H antiport. Collectively, these observations indicate that cyclic nucleotides modulate the Na/H antiporter in human platelets through their effect on thrombin-evoked changes in cytosolic free Ca. Presumably, this effect holds for other agonists which stimulate phospholipase C, raise cytosolic-free Ca, and activate the Na/H antiport through protein kinase C dependent and protein kinase C-independent mechanisms. (J.

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