title: Red cell sodium-lithium countertransport and cardiovascular risk factors in essential hypertension.
abstract: Human red blood cells possess a Na (+)H (+) antiporter in the plasma membrane that can exchange external Na(+) for intracellular H(+) when the intracellular pH falls below 7.0. The antiporter can also exchange Na(+) for Li(+) and that is named Na (+)Li (+) countertransport (SLC). This antiporter activity has been extensively investigated in essential hypertension and diabetes by clinical, epidemiologic, and genetic studies. Elevated values are found in patients with essential hypertension and diabetic nephropathy. In vitro studies in red cells of fasted individuals have demonstrated that physiologic doses of insulin increase the maximal transport rate and the K(m) for Na(+) of both Na (+)Li (+) and Na (+)H (+) exchanges. Ex vivo, SLC also exhibits elevated maximal activity and low affinity for Na(+) in insulin-resistant hypertensives. Patients with elevated antiporter activity manifest metabolic abnormalities (for example, high fasting insulin levels, hyperlipidemia, increased total body exchangeable Na(+), and renal and cardiac hypertrophy) that are part of the syndrome characterized by resistance to insulin-stimulated body glucose disposal. The coexistence of hypertension with insulin resistance and elevated SLC has suggested that a link between the metabolic and ion transport abnormalities may be mediated through chronic elevation of insulin levels. The association between circulating insulin concentrations and prevalence and severity of cardiovascular disease has been documented in many prospective population studies. Insulin modulation of this Na(+) antiporter might be an intermediate risk factor for cardiovascular disease that monitors chronic alterations of Na(+) homeostasis observed in hypertension and diabetes.
authors.affiliation: Mitzy Canessa is at the Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital Boston, MA 02115-5817, USA; Mitzy Canessa is at the Endocrine-Hypertension Division, Harvard Medical School, Boston, MA 02115-5817, USA.
authors.forename: M
authors.initials: M
authors.lastname: Canessa