title: Structural, functional, and molecular alterations produced by aldosterone plus salt in rat heart: association with enhanced serum and glucocorticoid-regulated kinase-1 expression.
abstract: We aimed to evaluate the structural, functional, inflammatory, and oxidative alterations, as well as serum and glucocorticoid-regulated kinase-1 (SGK-1) expression, produced in rat heart by aldosterone + salt administration. Fibrosis mediators such as connective tissue growth factor, matrix metalloproteinase 2, and tissue inhibitor of metalloproteinases 2 were also evaluated. Treatment with spironolactone was evaluated to prove mineralocorticoid mediation. Male Wistar rats received aldosterone (1 mg[middle dot]kg-1[middle dot]d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg[middle dot]kg-1[middle dot]d-1). Systolic and diastolic blood pressures, left ventricle (LV) systolic pressure, and LV end-diastolic pressure were elevated (P < 0.05) in aldosterone + salt-treated rats. In aldosterone + salt-treated rats, -dP/dt decreased (P < 0.05), but +dP/dt was similar in all groups. Spironolactone normalized (P < 0.05) systolic blood pressure, diastolic blood pressure, LV systolic pressure, LV end-diastolic pressure, and -dP/dt. Relative heart weight, collagen content, messenger RNA expression of transforming growth factor beta, connective tissue growth factor, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 2, tumor necrosis factor alpha, interleukin-1[beta], p22phox, endothelial nitric oxide synhtase, and SGK-1 were increased (P < 0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (P < 0.05). SGK-1 might be a key mediator in the structural, functional, and molecular cardiac alterations induced by aldosterone + salt in rats. All the observed changes and mediators are related with the activation of mineralocorticoid receptors.
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Fernández
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.forename: María
authors.initials: M
authors.lastname: Miana
authors.forename: Sandra
authors.initials: S
authors.lastname: Ballesteros
authors.forename: Carmen
authors.initials: C
authors.lastname: Delgado
authors.forename: Su
authors.initials: S
authors.lastname: Song
authors.forename: Thomas
authors.initials: T
authors.lastname: Hintze
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010770:Phosphotransferases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*; D013148:Spironolactone / Q000378:metabolism / Q000494:pharmacology*; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D017874:Immediate-Early Proteins; D007375:Interleukin-1; D020778:Matrix Metalloproteinase 2; D019255:NADPH Oxidases; D052250:Nitric Oxide Synthase Type III; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride; D013148:Spironolactone; D019716:Tissue Inhibitor of Metalloproteinase-2; D014409:Tumor Necrosis Factor-alpha; D000099184:Serum-Glucocorticoid Regulated Kinases; C515768:Cyba protein, rat