Original Article
Kidney International (2000) 58, 229–235; doi:10.1046/j.1523-1755.2000.00157.x
Red cell Na+/Li+ countertransport and Na+/H+ exchanger isoforms in human proximal tubules
Leong L Ng, Paulene A Quinn, Frease Baker and Susan J Carr
Department of Medicine, Leicester Royal Infirmary, and Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom
Correspondence: Leong L. Ng, M.D., Department of Medicine and Therapeutics, Level 4, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom. E-mail: lln1@le.ac.uk
Received 22 October 1999; Revised 27 January 2000; Accepted 10 February 2000.
Abstract
Red cell Na+/Li+ countertransport and Na+/H+ exchanger isoforms in human proximal tubules.
Background
Increased activity of the Na+/Li+ countertransporter (SLC) is a well-recognized intermediate phenotype of hypertension and diabetic nephropathy and may indicate a predisposition to hypertension. Previous work has attempted to link this membrane transport marker to altered Na+ reabsorption 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 tubule, respectively, we investigated the relationship between these transport proteins and red cell SLC to examine whether the peripheral blood transport phenotype is associated with altered levels of transport proteins in the proximal tubule.
Methods
Proximal tubules were prepared from human nephrectomy specimens. NHE-1 and NHE-3 were detected on Western blots by specific antibodies. Red cell SLC was also measured.
Results
Both NHE-1 and NHE-3 proteins were demonstrated, with molecular weights 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 NHE-3 and NHE-1 protein levels were significant predictors of red cell SLC, accounting 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 for the blunted pressure natriuresis and predisposition to hypertension.
Keywords:
sodium/hydrogen exchanger, sodium/lithium countertransport, hypertension, diabetic nephropathy, natriuresis
