CAN WE USE ERYTHROCYTES FOR THE STUDY OF THE ACTIVITY OF THE UBIQUITOUS NA+ H+ EXCHANGER (NHE-1) IN ESSENTIAL-HYPERTENSION/

Both Na+/Li+ countertransport and electrochemical proton gradient (Del ta mu(H)+)-induced Na+ and H+ fluxes are increased in erythrocytes fro m patients with essential hypertension. It was assumed that these abno rmalities are related to ubiquitous (housekeeping) forms of the Na+/H exchanger (NHE-1). To examine this hypothesis, we compared kinetic an d regulatory properties of erythrocyte Na+/Li+ countertransport and De lta mu(H)+-induced Na+ and H+ fluxes with data obtained for cloned iso forms of the Na+/H+ exchanger. In human erythrocytes, Na+/Li+ countert ransport exhibited a hyperbolic dependence on [Na+](o) with a K-0.5 of similar to 30 to 40 mmol/L. The activity of this carrier was increase d by two-fold in the fraction of erythrocytes enriched with the old ce lls, was inhibited by 0.1 mmol/L phloretin, and was insensitive to bot h 1 mmol/L amiloride and ATP depletion. In contrast, Delta mu(H)+-indu ced Na-22 influx was exponentially increased at [Na+](o) > 60 mmol/L, was insensitive to phloretin, was partly decreased by both 1 mmol/L am iloride and ATP depletion, and was the same in total erythrocytes and in the old cells. The values of Na+/Li+ countertransport and Delta mu( H)+-induced Na+ influx in erythrocytes from different species were not correlating and their ratio in human, rat, and rabbit erythrocytes wa s 10:1:170 and 1:5:1 for Na+/ Li+ countertransport and Delta mu(H)+-in duced Na+ influx, respectively. In contrast to the majority of nonepit helial cells and cells transfected with an ubiquitous isoform of Na+/H + exchanger, both Delta mu(H)+-induced Na+ influx and Na+/Li+ countert ransport in human erythrocytes were completely insensitive to ethyliso propyl amiloride (20 mu mol/L) and cell shrinkage. Thus, our data stro ngly suggest that human erythrocyte Na+/Li+ countertransport and Delta mu(H)+-induced Na+/H+ exchange are mediated by the distinct transport ers. Moreover, because the properties of these erythrocyte transporter s and NHE-1 are different, it complicates the use of erythrocytes for the identification of the mechanism for activating the ubiquitous form of Na+/H+ exchanger in primary hypertension. Am J Hypertens 1998;11:7 74-783 (C) 1998 American Journal of Hypertension, Ltd.