Protective effects of cyclosporine A on myocardial damage and fibrosis induced by isoproterenol via ET pathway

Abstract

Abstract: AIM: To investigate the protective effects of Cyclosporine A (CsA) on myocardial damage and fibrosis induced by isoproterenol (Iso) in rats and the role of ET pathway.METHODS: Myocardial damage and fibrosis in rats were produced by isoproterenol (2 mg°kg^-1 °d^-1, s.c.) for 10 days.In CsAtreated group, the rats were pretreated by CsA (25 mg/kg, s.c.).All the animals were subjected to cannulation through left carotid artery to measure LVSP, LVEDP, and±dp dtmax under urethane anesthesia. The contents of hydroxyproline (Hyp) in the left ventricle was assayed.The expressions of ET-1, ETAR, CTGF and MMP-9 mRNA were measured by RT-PCR and ETAR and MMP-9 protein were measured by western blotting.RESULTS: Compared with the control group, impaired cardiac function, elevated Hyp, and upregulation of ET-1, ETAR, CTGF and MMP-9 in mRNA and ETAR and MMP-9 in protein were found in Iso treated group.Pretreatment with CsA these changes were attenuated.CONCLUSION: CsA can alleviate myocardial damage and fibrosis induced by Iso in rats, and this effect is, at least in part, mediated by the ET pathway.

Key words: CyclosporineA, endothelin-1, endothelinAreceptor, connectivetissuegrowthfactor, matrixmetalloproteinase9

CLC Number:

R965.2

PENG Hong-jun, JI Hui, DAI De-zai, DAI Yin. Protective effects of cyclosporine A on myocardial damage and fibrosis induced by isoproterenol via ET pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 966-971.

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