Abstract
BACKGROUND: Fibrosis results in excessive accumulation of extracellular matrix proteins, collagen component alteration, and abnormalities in structure and is partly derived from a process called the endothelial-mesenchymal transition involving transforming growth factor β (TGF-β). We investigated whether spironolactone, an aldosterone receptor blocker, attenuated isoprenaline (Iso)-induced heart failure in rats and also studied the mechanism for the same. METHODS: Sprague-Dawley rats were subcutaneously injected with Iso to induce heart failure, which promoted renal fibrosis; rats with spironolactone treatment were given a gavage of spironolactone (30 or 60 mg/kg/d, for 21 days). Cardiac function and fibrosis indices were measured. Pathological alterations and expression of Type I and III collagen, α-smooth muscle actin, cluster of differentiation-31, and TGF-β were examined. RESULTS: In Iso-induced heart failure in rats, spironolactone significantly improved cardiac function and decreased myocardial fibrosis, reduced collagen fibrous proliferation in kidney, reduced expression of Type I and III collagen, increased the expression of cluster of differentiation-31, and decreased the expression of α-smooth muscle actin and TGF-β. CONCLUSION: Spironolactone may prevent renal fibrosis by inhibiting the endothelial-mesenchymal transition.