Aldosterone and cardiac fibrosis: in vitro studies

Abstract

Aldosterone does not exert a direct effect on collagen synthesis in rat cardiac fibroblasts grown in culture. The increased cardiac collagen observed in vivo in aldosterone treated, salt loaded rats may thus represent secondary effects of aldosterone in this model.

Mechanisms of Mineralocorticoid Action

“…75 Whether or not aldosterone acts directly on cardiac fibroblasts is unclear, with some investigators showing direct anabolic effects (collagen production), 80 whereas others have not. 81 Recently, Pratt et al suggested that aldosterone can promote proliferation of cardiac fibroblasts by activating specific cellular signaling cascades such as k-Ras and the MAPK1/2 cascade. In these studies, physiological concentrations of aldosterone (10 nmol/L) induced significant increases in cardiac fibroblast proliferation, an effect that was blocked by spironolactone.…”

“…81 In the mouse, it is suggested that 11␤HSD1 expression is predominantly in VSMCs, whereas 11␤HSD2 is localized in endothelial cells. 87 11␤HSD2 is thus appropriately situated to modulate endothelial cell function, even though endothelial dysfunction in 11␤HSD2 knockout mice cannot be explained simply by the presence of increased access of corticosterone to endothelial cell corticosteroid receptors, indicating additional mechanisms.…”

Antifibrogenic effects of canrenone, an antialdosteronic drug, on human hepatic stellate cells

“…Although initial reports indicated that aldosterone induces transcrip-tion of procollagen I messenger RNA and increases collagen I synthesis in rat cardiac fibroblasts, 9,10 other studies could not confirm these findings. 11,12 To further reinforce the concept that aldosterone does not promote, at least directly, tissue fibrosis, recent work by Rombouts et al, 13 performed in rat cardiac fibroblasts metabolically labeled with [ 35 S]methionine/[ 35 S]cysteine, has confirmed that this hormone does not affect de novo collagen synthesis at physiological concentrations (10 Ϫ8 to 10 Ϫ10 mol/L), whereas an inhibitory effect is observed at 10 Ϫ7 mol/L. In addition, the same group of investigators has also shown that aldosterone does not promote de novo collagen synthesis in activated rat hepatic stellate cells (HSC), a cell type that contributes to the progression of liver fibrosis after chronic liver tissue damage 14 and is potentially involved in the genesis of portal hypertension.…”

A Selective Antagonist of Mineralocorticoid Receptor Eplerenone in Cardiology Practice

“…Как уже отмечалось выше, значительную роль в патофизиологии сердечной не-достаточности играет повышение уровня альдостеро-на, а также кортизола [24,25], поэтому у таких пациентов увеличено количество рецепторов минералокорти-коидов в ткани миокарда [26,27]. Несмотря на терапию ингибиторами АПФ/АРА и бета-адреноблокаторами, у пациентов даже с «мягкими» проявлениями сердеч-ной недостаточности чаще всего наблюдаются повы-шенные уровни альдостерона и кортизола крови [28][29][30][31][32][33]. Ни ингибиторы АПФ/АРА, ни бета-адреноблока-торы не оказывают блокирующего действия на эти ре-цепторы.…”