Brearley C J, Wood A J, Aronson J K, Grahame-Smith D G
MRC Unit, Radcliffe Infirmary, Oxford, UK.
J Hypertens. 1993 Feb;11(2):147-53. doi: 10.1097/00004872-199302000-00006.
To study the activity of the sodium-lithium (Na(+)-Li+) countertransport system in vivo in the erythrocytes of patients with untreated essential hypertension.
Lithium substitutes for sodium efflux in the sodium-sodium (Na(+)-Na+) countertransport system. In essential hypertension the efflux of lithium from cells in vitro has been used as a measure of the activity of the Na(+)-Na+ countertransporter and has been shown to be increased. We administered oral lithium and used its disposition in erythrocytes to measure Na(+)-Li+ countertransporter activity in vivo.
Ten men with essential hypertension who had never taken any antihypertensive treatment were matched with 10 male controls for age, weight, and plasma and erythrocyte sodium and potassium concentrations.
Repeated measurements were made of plasma and intra-erythrocytic lithium concentrations during the 48h after the oral administration of 16.2 mmol lithium carbonate. Data were analysed using standard pharmacokinetic techniques.
The rate of lithium efflux from the erythrocytes was increased in all patients with hypertension and in none of the normotensive controls. Hill plots derived from in vivo activation curves for erythrocytic Na(+)-Li+ countertransport showed that the normotensive participants had a Hill slope of 1 (SD 0.1), whereas the hypertensives had a Hill slope of 3.2 (SD 1.0).
The activity of the Na(+)-L+ countertransport system is increased in untreated essential hypertension in vivo; this confirms in vitro findings. A new finding is that there is a change in either the stoichiometry or the co-operativity of lithium efflux via the Na(+)-L+ countertransport system, suggesting that the rate of sodium efflux may be greater than that of influx in the cells of people with hypertension.
研究未经治疗的原发性高血压患者红细胞中钠-锂（Na(+)-Li+）逆向转运系统在体内的活性。
在钠-钠（Na(+)-Na+）逆向转运系统中，锂替代钠外流。在原发性高血压中，体外细胞中锂的外流已被用作Na(+)-Na+逆向转运体活性的指标，且已显示其活性增加。我们口服锂并利用其在红细胞中的分布来测量体内Na(+)-Li+逆向转运体的活性。
10名从未接受过任何抗高血压治疗的原发性高血压男性患者与10名男性对照在年龄、体重、血浆及红细胞钠和钾浓度方面进行匹配。
口服16.2 mmol碳酸锂后48小时内，对血浆和红细胞内锂浓度进行重复测量。数据采用标准药代动力学技术进行分析。
所有高血压患者红细胞中锂的外流速率均增加，而正常血压对照组无一增加。从红细胞Na(+)-Li+逆向转运的体内激活曲线得出的希尔图显示，正常血压参与者的希尔斜率为1（标准差0.1），而高血压患者的希尔斜率为3.2（标准差1.0）。
未经治疗的原发性高血压患者体内Na(+)-Li+逆向转运系统的活性增加；这证实了体外研究结果。一个新发现是，通过Na(+)-Li+逆向转运系统的锂外流在化学计量或协同性方面存在变化，这表明高血压患者细胞中钠的外流速率可能大于内流速率。
