title: Sodium-proton exchange and primary hypertension. An update.
abstract: An enhancement of sodium-proton exchange in blood cells of patients with primary hypertension has been described by various investigators. The present review summarizes some of the most recent findings regarding the enhanced sodium-proton exchanger activity in primary hypertension and discusses the potential mechanisms that may contribute to or explain these findings. Novel evidence has been accumulated on the in vivo regulation of the sodium-proton exchanger in humans, and recent findings suggest that metabolic acidosis, high NaCl intake, and circulating hormones (eg, insulin) can enhance sodium-proton exchanger activity in blood cells. However, the relative roles of such exogenous factors in the stimulation of sodium-proton exchanger activity in primary hypertension remain questionable because enhanced sodium-proton exchanger activity persists in immortalized lymphoblasts from patients with primary hypertension after prolonged cell culture. Therefore, at least in a certain group of hypertensive subjects this abnormality cannot be due to metabolic or hormonal alterations of the "hypertensive" in vivo milieu but appears to be under genetic control. Available evidence strongly argues against intrinsic changes of the sodium-proton exchanger protein itself in primary hypertension, for example, a mutation in the encoding gene. Interestingly, immortalized cells from hypertensive subjects with enhanced sodium-proton exchanger activity display a distinctly enhanced proliferation pattern that appears to be independent of this ion transport. At present we speculate that enhanced sodium-proton exchanger activity and proliferation may represent indicators of a genetically fixed enhanced intracellular signal transduction in primary hypertension that may be caused by an increased activation of pertussis toxin-sensitive G proteins.
authors.affiliation: Institut für Pharmakologie, Universitätsklinikum, Essen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Siffert
authors.forename: R
authors.initials: R
authors.lastname: Düsing
mesh_terms: D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism; D010641:Phenotype; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D017923:Sodium-Hydrogen Exchangers