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.

The Effects of Adiponectin and Leptin on Human Endothelial Cell Proliferation: A Live-Cell Study

“…By contrast, it has been reported that this adipokine is able to reduce endothelial cell migration induced by VEGF [32,38]. Moreover, different studies have suggested that adiponectin can act as a chemotactic agent of endothelial cells [27,28]. Therefore, it seems that adiponectin can exert a different effect on endothelial cell migration, depending on the conditions.…”

“…RNAs were frozen at –80°C until their use. One microgram of RNA was taken to perform reverse transcription as previously described [28]. Real-time polymerase chain reaction was performed using a fluorescence temperature cycler (SmartCycler; Cepheid, Sunnyvale, Calif., USA).…”

“…Real-time polymerase chain reaction was performed using a fluorescence temperature cycler (SmartCycler; Cepheid, Sunnyvale, Calif., USA). Gene expression was quantified using TaqMan™ probes and primers for leptin receptor and 18S (Roche) and adiponectin receptor types 1 and 2 (Applied Biosystems) as previously reported [28]. The 2 – ΔΔ CT method was used in order to analyze relative changes in gene expression from real-time quantitative PCR experiments [29].…”

Avances en la etiopatogenia de la hipertensión arterial: actualización en la investigación preclínica

“…Reducciones de las alteraciones cardiacas inflamatorias y el estrés oxidativo asociadas a la hipertensión [32][33] Aldosterona Fibrosis e hipertrofia cardiaca, aumento de la densidad de corriente de canales de Ca2+ tipo L, prolongación de la duración del potencial de acción, aumento de la PAS y PAD 34,35 SGK-1 Alteraciones cardiacas relacionadas con la aldosterona 36 Cardiotrofina 1 Enfermedades cardiacas a través de mecanismos dependientes de hipoxia.…”

Mineralocorticoid regulation of cell function: the role of rapid signalling and gene transcription pathways

“…Several profibrotic genes are directly regulated by MR as a transcription factor. As in the kidney, MR increases SGK1 transcription in the heart (Martin-Fernandez et al 2011). SGK1 upregulates the profibrotic CTGF (Vallon et al 2006, Terada et al 2012, and the importance of SGK1 in the pathogenesis of MR-mediated cardiac fibrosis has been established in a knockout mouse model (Vallon et al 2006).…”