title: Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart.
abstract: Liberal or high-sodium (HS) intake, in conjunction with an activated renin-angiotensin-aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT(1)R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1.6% Na(+)) and low-sodium (LS; 0.02% Na(+)) rat chow was fed to male healthy Wistar rats (n=7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT(1)R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT(1)R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT(1)R-CAV-3 and MR-CAV-3 complexes, but increased immunoprecipitation of AT(1)R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.
authors: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA. vricchiuti@partners.org
authors: Vincent
authors: V
authors: Ricchiuti
authors: Nathalie
authors: N
authors: Lapointe
authors: Luminita
authors: L
authors: Pojoga
authors: Tham
authors: T
authors: Yao
authors: Loc
authors: L
authors: Tran
authors: Gordon H
authors: GH
authors: Williams
authors: Gail K
authors: GK
authors: Adler
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000187:drug effects / Q000502:physiology; D051244:Caveolin 3 / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D051242:Caveolin 1; D051244:Caveolin 3; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D012982:Sodium, Dietary