Erythrocyte sodium-lithium countertransport: another link between essential hypertension and diabetes

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.