title: Topics on the Na+/Ca2+ exchanger: role of vascular NCX1 in salt-dependent hypertension.
abstract: Excess salt intake is a major risk factor for hypertension. However, the molecular mechanisms underlying salt-dependent hypertension remain obscure. Our recent studies using selective Na(+)/Ca(2+) exchange inhibitors and genetically engineered mice provide compelling evidence that salt-dependent hypertension is triggered by Ca(2+) entry through Na(+)/Ca(2+) exchanger type 1 (NCX1) in arterial smooth muscle. Endogenous cardiac glycosides, which may contribute to salt-dependent hypertension, seem to be necessary for NCX1-mediated hypertension. Intriguingly, recent studies by Dostanic-Larson et al. using knock-in mice with modified cardiac glycoside binding affinity of Na(+),K(+)-ATPases demonstrate that this binding site plays an important physiological role in blood pressure control. Thus, when cardiac glycosides inhibit Na(+),K(+)-ATPase in arterial smooth muscle cells, the elevation of local Na(+) on the submembrane area is believed to facilitate Ca(2+) entry through NCX1, resulting in vasoconstriction. This proposed pathway may have enabled us to explain how to link dietary salt to hypertension.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Japan. tiwamoto@cis.fukuoka-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002301:Cardiac Glycosides / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D012965:Sodium Chloride; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002301:Cardiac Glycosides; D017673:Sodium Chloride, Dietary; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D012965:Sodium Chloride; D002118:Calcium