Plasma lipids affect maximum velocity not sodium affinity of human sodium‐lithium countertransport: distinction from essential hypertension

Abstract

Inheritance is a major determinant of increased sodium-lithium countertransport (SLC) activity in hypertension. However, hyperlipidaemia can also cause increased SLC activity in some individuals and it is difficult to distinguish this effect from the effect of hypertension. Erythrocyte SLC activity and its kinetic determinants sodium affinity (km) and maximum velocity (Vmax) were measured in 25 hyperlipidaemic patients and 15 normal controls (NC). Increased SLC activity (0.31 +/- SEM 0.03 mmol Li/(h x 1 cells) vs. NC 0.20 +/- 0.01, P < 0.01) in the hyperlipidaemic patients was associated with increased Vmax (0.59 +/- 0.07 vs. NC 0.41 +/- 0.03, P < 0.01) but normal km (median 120 range [40-324] mmol l-1 vs. 140 [108-260]. Lipid-lowering therapy resulted in decreased SLC activity secondary to a fall in Vmax. Km remained constant despite the changes in lipids and Vmax. The mechanism of increased SLC activity in hyperlipidaemia is different from that in essential hypertension where increased sodium affinity is found. Measurement of the kinetic characteristics of SLC may discriminate between the independent influences of hypertension and hyperlipidaemia on the sodium-lithium countertransporter.

Kinetic characteristics of the erythrocyte sodium-lithium countertransporter in black normotensive subjects compared with three other ethnic groups

“…19,22 More recent work has demonstrated that it is the V max of the countertransporter which is sensitive to plasma lipid status; with emphasis on HDL cholesterol and plasma triglyceride concentrations. 29 Despite the present study finding no correlation between triglyceride concentration and V max values in the black group, the lower triglyceride concentration in these subjects, noted on several occasions previously, [30][31][32] may still be relevant. Although the present study failed to detect any differences between the ethnic groups with respect to plasma HDL-cholesterol, this plasma lipoprotein tends to be elevated in black subjects.…”

Thiol Protein Defect in Sodium-Lithium Countertransport in Subset of Essential Hypertension

“…9 Thus, changes in maximum velocity (V max ) or ion binding events (K m or V max /K m ) cannot be discriminated and may be missed. Kinetic studies of Na/Li CT showed that whereas hyperlipidemia increased V max , 10 the defect in EHT was a low K m for sodium at the external site. 11 However, a molecular explanation for this abnormality is still awaited.…”

Abnormalities of membrane function and lipid metabolism in hypertension A review

“…Ion transport alterations are often associated with abnormal lipid metabolism, as can be illustrated for the Na ϩ -Li ϩ countertransport system. Its kinetic properties are dependent on membrane lipid composition [73][74][75] and its increased activity in erythrocytes of hyperlipidemic or hypertensive patients 76 -78 can be reduced by lipid-lowering therapy.74 Dietary modification of erythrocyte membrane lipid composition affects various Na ϩ transport systems, including Na ϩ -K ϩ pump, NaϪ cotransport, Na ϩ leak, and partially also Na ϩ -Li ϩ countertransport. 79,80 Na ϩ -Li ϩ countertransport activity is inversely related to the membrane content of polyunsaturated fatty acids 28,73,81 and also depends on the amount and distribution of cholesterol 28,81,82 as well as on the content of particular classes and molecular species of phospholipids in erythrocyte membranes.…”