Papel de la quinasa regulada por suero y glucocorticoides 1 en las alteraciones cardiacas producidas por la aldosterona en ratas

Abstract

Introduction: Aldosterone induces cardiac hypertrophy and it is known to induce serum and glucocorticoid regulated kinase 1 (SGK-1) gene expression. Aim: We aimed to evaluate structural, functional, inflammatory and oxidative alterations, as well as serum and glucocorticoid regulated kinase1 (SGK-1) expression, produced in rat heart by aldosterone + salt administration. Treatment with spironolactone was evaluated to prove mineralocorticoids mediation. Matherial and methods: Male Wistar rats received aldosterone (1 mg/kg/day) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg/kg/day). At the end of treatment hemodynamics were measured: SBP, DBP, LVEDP, LVSP, +dP/dt and �dP/dt. Heart relative weight was measured as cardiac hypertrophy index. mRNA expression of TGF-ß, CTGF, MMP2, TIMP2, TNF-a,IL-1ß, p22phox, eNOS and SGK-1 were measured. Cardiac collagen content was measured by histological techniques. Results: SBP and DBP, LVSP and LVEDP were elevated (P < .05) in aldosterone + salt-treated rats. �dP/dt decreased (P < .05) in aldosterone + salt-treated rats, but +dP/dt was similar in all groups. Spironolactone normalized (P < .05) SBP, DBP, LVSP, LVEDP and �dP/dt. Relative heart weight, collagen content, mRNA expression of TGF-ß, CTGF, MMP2, TIMP2, TNF-a, IL-1ß, p22phox, eNOS and SGK-1 were increased (P < .05) in aldosterone + salt-treated rats, being reduced by spironolactone (P < .05). Conlusions: 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 activation of mineralocorticoid receptors.