Raised Affinity for Extracellular Sodium of the Sodium-Lithium Countertransporter is Associated with a Family History of Hypertension and Uraemia in Patients with Renal Disease

Abstract

1. Increased affinity for sodium (Km) at an external site of the sodium-lithium countertransporter and altered membrane microviscosity in the surface regions of the lipid bilayer identifies a group of essential hypertensive patients with a genetic predisposition to hypertension. The present study investigated the kinetic properties of the sodium-lithium countertransporter and membrane microviscosity in patients with hypertension, renal disease and impaired renal function. 2. Sixty patients with renal disease (28 chronic renal failure, 30 hypertensive, 23 family history of hypertension) were investigated. Standard erythrocyte sodium-lithium countertransport activity, sodium affinity constant (Km), maximum reaction velocity (Vmax) and membrane microviscosity were measured. 3. Patients with renal disease and a family history of hypertension had significantly lower Km (P < 0.05) values and raised membrane microviscosity measured by 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy (P < 0.05) compared with patients without a family history of hypertension. 4. Uraemic subjects had low K(m) values compared with patients with renal disease and normal renal function (P < 0.05). However, there was no significant difference in membrane microviscosity between uraemic and non-uraemic subjects. 5. In patients with a family history of hypertension, sodium-lithium countertransport activity and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy are important markers of cellular changes in essential hypertension, independent of renal disease. Uraemia, independently of hypertension, produces an alteration in the function of the sodium-lithium countertransporter which has previously been associated with a genetic predisposition to hypertension and cardiovascular disease.

Biomarkers in disease and health

“…An increased affinity for sodium at an external site of the sodium -lithium counter transporter has been associated with a genetic predisposition to hypertension and to cardiovascular disease (Carr et al 1997). An association between left ventricular hypertrophy and cardiovascular disease has been found and there appears to be some genetic component in this condition (Lauer, 1995).…”

Sodium/lithium countertransport and intracellular calcium concentration in patients with essential hypertension and coronary heart disease

“…Essential hypertension is associated with several abnormalities in cellular ion transport systems, including Na + \Li + countertransport (Na + \Li + CT) [1][2][3][4][5][6][7][8], Na + \H + exchange [3,[9][10][11][12][13][14], Na + -K + co-transport [6,15], and intracellular Ca# + signalling [9,12,[15][16][17]. Several of these abnormalities have been shown to be particularly frequent in subsets of subjects with hypertension, giving rise to the hypothesis that they may be associated with hypertension-induced end-organ damage rather than with hypertension per se [18,19].…”

Sodium/lithium countertransport and intracellular calcium concentration in patients with essential hypertension and coronary heart disease

“…Essential hypertension is associated with several abnormalities in cellular ion transport systems, including Na + \Li + countertransport (Na + \Li + CT) [1][2][3][4][5][6][7][8], Na + \H + exchange [3,[9][10][11][12][13][14], Na + -K + co-transport [6,15], and intracellular Ca# + signalling [9,12,[15][16][17]. Several of these abnormalities have been shown to be particularly frequent in subsets of subjects with hypertension, giving rise to the hypothesis that they may be associated with hypertension-induced end-organ damage rather than with hypertension per se [18,19].…”