Canessa M
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Curr Opin Nephrol Hypertens. 1994 Sep;3(5):511-7. doi: 10.1097/00041552-199409000-00006.
Erythrocyte Na+/Li+ countertransport has been extensively investigated in human essential hypertension in numerous clinical, epidemiologic, and genetic studies and through these studies has emerged as the best-characterized intermediate phenotype. Patients with elevated antiporter activity manifest high total body exhangeable Na+ levels, renal and cardiac hypertrophy, and metabolic abnormalities which are part of the syndrome characterized by resistance to insulin-stimulated body glucose disposal. The coexistence of hypertension with insulin resistance and elevated Na+/Li+ countertransport has suggested that a link between the metabolic and ion transport abnormalities may be mediated through elevated insulin levels. In vitro studies in erythrocytes of fasted individuals have demonstrated that physiologic doses of insulin increased the maximal transport rate and the concentration for half-maximal transport for Na+ of both the Na+/Li+ and Na+/H+ exchanges. In vivo, Na+/Li+ exchange also exhibits a low affinity for Na+ in insulin-resistant hypertensive patients and in patients with insulin-dependent diabetes mellitus complicated by nephropathy. Insulin modulation of this antiporter may play a role in the chronic alterations in Na+ homeostasis observed in hypertension and diabetes.
在众多临床、流行病学和遗传学研究中，对人类原发性高血压患者的红细胞钠/锂逆向转运进行了广泛研究，通过这些研究，它已成为特征最明确的中间表型。钠/锂逆向转运体活性升高的患者表现出全身可交换钠水平升高、肾和心脏肥大以及代谢异常，这些都是以胰岛素刺激的机体葡萄糖代谢抵抗为特征的综合征的一部分。高血压与胰岛素抵抗以及钠/锂逆向转运升高并存，这表明代谢异常与离子转运异常之间的联系可能是通过胰岛素水平升高介导的。对空腹个体红细胞的体外研究表明，生理剂量的胰岛素可提高钠/锂和钠/氢交换的最大转运速率以及钠半最大转运浓度。在体内，胰岛素抵抗的高血压患者以及患有胰岛素依赖型糖尿病并发肾病的患者中，钠/锂交换对钠也表现出低亲和力。胰岛素对这种逆向转运体的调节可能在高血压和糖尿病中观察到的钠稳态慢性改变中起作用。
