Na–Li Countertransport Kinetics in the Relatives of Hypertensive Patients with Abnormal Na–Li Countertransport Activity

Abstract

Familial factors are believed to be important in determining the high sodium–lithium countertransport activity (defined as >0.40 mmol Li/(h × l cell) at external sodium concentration of 140 mmol/L (Na_e140)) 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 (Na_e140) in essential hypertension is mainly due to a low Michaelis constant (K_m) and is associated with a highV_max/K_mratio. In contrast, dyslipidemias affectV_max. This study aimed to determine if there was evidence thatK_mandV_max/K_mratios 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 reducedK_mand increasedV_max/K_mcompared to normal subjects. Eleven relatives had high sodium–lithium countertransport activity (Na_e140), associated with lowK_mand highV_max/K_m. 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 theK_mandV_max/K_mof 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.