Na-Li countertransport kinetics in the relatives of hypertensive patients with abnormal Na-Li countertransport...

Familial factors are believed to be important in determining the high sodium-lithium countertransport activity (defined as >0.40 mmol Li/(h x l cell) at external sodium concentration of 140 mmol/L (Nae 140)) which is observed in a proportion of patients with essential hypertension. However, environmental factors such as pregnancy and dyslipidemia also affect activity. High sodium-lithium countertransport activity (Nae 140) in essential hypertension is mainly due to a low Michaelis constant (Km) and is associated with a high Vmax/Km ratio. In contrast, dyslipidemias affect Vmax. This study aimed to determine if there was evidence that Km and Vmax/Km ratios are influenced by familial factors. Sodium-lithium countertransport kinetics were measured in the 47 first degree relatives of 12 hypertensive probands with abnormal sodium-lithium countertransport kinetics and 35 normotensive control subjects. Sodium-lithium countertransport was measured as Na-stimulated Li efflux from lithium loaded erythrocytes. The relatives had significantly reduced Km and increased Vmax/Km compared to normal subjects. Eleven relatives had high sodium-lithium countertransport activity (Nae 140), associated with low Km and high Vmax/Km. The 14 relatives that were hypertensive had abnormalities of sodium-lithium countertransport kinetics. The results of this study suggest that familial factors are important in determining the Km and Vmax/Km of sodium-lithium countertransport activity. Studies aimed at determining the inheritance of sodium-lithium countertransport and its use as an intermediate phenotype of essential hypertension must measure its kinetic determinants to reduce the risk of confounding effects from other variables.