Abstract

Li-kun Ma*, Li-feng He, Bing-yu Zhang and Jing-sheng Hua

In this study, we investigated the effects of atorvastatin on aldosterone induced myocardial fibrosis in rat model and its potential mechanism. Forty male rats underwent right nephrectomy, and then, were given free access to 1% NaCl for 4 weeks. During this period, rats were randomly divided into 4 groups; vehicle group (CON group: Subcutaneous injection of saline); aldosterone treated group (ALD group: Aldosterone 18 g*d-1 subcutaneously); spironolactone plus aldosterone treated group (SPI+ALD group: Aldosterone 18 g*d -1 subcutaneously plus spironolactone 20 mg*kg-1 *d-1 intravenously); atorvastatin plus aldosterone treated group (ATO+ALD group: Aldosterone 18 g.d-1 subcutaneously plus Atorvastatin 50 mg*kg-1 *d-1 intravenously). Blood pressure was measured through catheterization. Myocardial collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyzed by Sirius-Red staining. The expressions of platelet-derived growth factor (PDGF-A, PDGF- B), platelet-derived growth factor receptor (PDGFR- , PDGFR- ), ectodermal dysplasia-1 (ED-1) and myocardial osteopontin were determined. Mean arterial blood pressure in rats receiving drug treatment was markedly elevated compared with the CON group (P < 0.01 or P < 0.05). Rats in ALD group had pronounced myocardial fibrosis and dramatically increased CVF and PVCA when compared with the other three groups. There were no significant differences between SPI+ALD group and ATO+ALD group in the CVF and PVCA. The expressions of PDGF-A, PDGF -B, PDGFR - , ED -1 and OPN in the ALD group were markedly higher than in the other three groups (P < 0.01 or P < 0.05), and no significant difference was observed between SPI+ALD group and ATO+ALD group in the expressions of PDGF- A, PDGF-B, PDGFR- and OPN. But the ATO+ALD group had lower ED-1 expression than SPI+ALD (P < 0.05). Furthermore, there was no significant difference in the PDGFR- expression among four groups. Atorvastatin may attenuate myocardial fibrosis, induced by aldosterone, in which the reduced macrophage infiltration and alleviated expressions of inflammatory cytokines, and platelet-derived growth factors and their receptors play critical roles.