Correlations of Na⁺-Li⁺ Exchange Activity with Na⁺ and Li⁺ Binding and Phospholipid Composition in Erythrocyte Membranes of White Hypertensive and Normotensive Individuals: A Nuclear Magnetic Resonance Investigation

Enhanced Na⁺-Li⁺ exchange activity has been reported in red blood cells (RBCs) of white patients with essential hypertension compared with RBCs of normotensive individuals. To understand the factors responsible for this finding, we applied novel and conventional spectroscopic and kinetic methods to blood samples from 10 hypertensive and 10 normotensive individuals. We measured the kinetic parameters (V_std, V_maxand K_m) for RBC Na⁺-Li⁺ exchange by atomic absorption spectrophotometry and used ²³Na and ⁷Li nuclear magnetic resonance relaxation methods to measure Na⁺ and Li⁺ binding to RBC membranes as well as ³¹P nuclear magnetic resonance spectroscopy to measure membrane phospholipid compositions. We found significant differences between the two groups for the affinity of Na⁺ for the RBC membrane (0.202±0.054 mmol/L^-1 for hypertensive patients versus 0.296±0.071 mmol/L^-1 for normotensive subjects, P<.005). The kinetic parameters of RBC Na⁺-Li⁺ exchange (V_std, V_max, and K_m) were 0.32±0.09 and U.66±0.17 mmol Li⁺/L cell ·h and 160±62 mmol/L, respectively, for hypertensive patients versus 0.21±0.06 and 0.32±0.14 mmol Li⁺VL cell · h and 86±69 mmol/L for normotensive subjects (P<.05). The fractions of phosphatidylserine and phosphatidylethanolamine were 0.153±0.009 and 0.294±0.016 for hypertensive patients versus 0.138±0.013 and 0.325±0.018 for normotensive subjects (P<.05). The Na⁺ binding constants were negatively correlated with the K^m values for both the hypertensive (r=-.61, P=.01) and normotensive (r= -.43, P=.04) groups. Changes in lipidprotein interactions in the RBC membranes of hypertensive patients appear to be responsible for weaker Na⁺ binding to the membrane and for the faster rates of RBC Na⁺-Li⁺ exchanee.