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.
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.
Carr
S J
SJ
Department of Nephrology, Leicester General Hospital, U.K.
Moore
D
D
Sikand
K
K
Norman
R I
RI
D017920:Antiporters / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000502:physiology; D005192:Family Health; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*; D014783:Viscosity
D017920:Antiporters; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium