title: Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure.
abstract: Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+homeostasis are unfavorable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL as contributing to the pathophysiology of salt-sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow Cardiovascular and Medical Sciences, Glasgow, United Kingdom; and Lesley.Graham@glasgow.ac.uk.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Graham
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow Cardiovascular and Medical Sciences, Glasgow, United Kingdom; and.
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Ferreri
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D001794:Blood Pressure / Q000502:physiology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008138:Loop of Henle / Q000033:anatomy & histology / Q000502:physiology* / Q000503:physiopathology; D000074083:Sodium-Hydrogen Exchanger 3 / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism; D058949:Uromodulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D027682:Cation Transport Proteins; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D064466:Solute Carrier Family 12, Member 1; D058949:Uromodulin
keywords: hypertension; salt sensitivity; sodium, kidney; thick ascending limb of the loop of Henle