Red cell Na+/Li+ countertransport and Na+/H+ exchanger isoforms in human proximal tubules

Background. Increased activity of the Na+/Li+ counter-transporter (SLC) is a well-recognized intermediate phenotype of hypertension and diabetic nephr opathy and may indicate a predisposition to hypertension. Previous work has attempted to link this membrane transport marker to altered Na+ reabsorpti on in the proximal tubule. Since the Na+/H+ exchanger (NHE) isoforms 1 and 3 are expressed in the basolateral and apical membranes of the proximal tub ule, respectively, we investigated the relationship between these transport proteins and red cell SLC to examine whether the peripheral blood transpor t phenotype is associated with altered levels of transport proteins in the proximal tubule. Methods. Proximal tubules were prepared from human nephrectomy specimens. N HE-1 and NHE-3 were detected on Western blots by specific antibodies. Red c ell SLC was also measured. Results. Both NHE-1 and NHE-3 proteins were demonstrated, with molecular we ights of 97 and 85 kD, respectively. SLC was very strongly correlated with the level of NHE-3 protein (r = 0.78, P < 0.001) and was negatively related to NHE-1 protein (r = -0.32). In multiple regression analysis, only NWE-3 and NHE-1 protein levels were significant predictors of red cell SLC, accou nting for up to about 70% of the variance of this parameter. Conclusions. We conclude that red cell SLC may be a marker of increased NHE -3 protein expression in the proximal tubule, which may account fur the blu nted pressure natriuresis and predisposition to hypertension.