IngentaConnect Improvement of chronic heart failure by dexamethasone is not asso...

Authors: XIA, Qin-gui; NA, Tao¹; GUO, Yi-min²; BI, Yun-tian²; ZHANG, Hai-yan²; DAI, De-zai

Source: Acta Pharmacologica Sinica, Volume 28, Number 2, February 2007 , pp. 202-210(9)

Abstract:

Aim: To demonstrate the hypothesis that dexamethasone (Dex) could improve chronic heart failure (CHF) by inhibiting the downstream signaling transduction of leptin but had no influence on the upregulation of leptin and its receptor in myocardium. Methods: CHF was induced by left coronary artery ligation for 6 weeks. CHF rats were treated with Dex 50 mg·kg^-1·d^-1. Hemodynamics, histology, reactive oxygen species (ROS)-related parameters, and leptin concentrations in serum were measured. The mRNA expression of matrix metalloproteinases (MMP) 2/9, tissue inhibitor of metalloproteinases (TIMP)1/2, tumor necrosis factor (TNF)-α, and OB-Rb were measured by RT-PCR. Results: In the CHF rats, hemodynamic functions were deteriorated, which was accompanied with myocardium remodeling and histological changes. CHF rats showed hyperleptinemia and excessive ROS in the serum, and the upregulation of MMP-2/9, TNF-α, and leptin receptor mRNA and downregulation of TIMP-1/2 mRNA in the myocardium compared with the sham operation group. Dex treatment significantly ameliorated CHF in association with the reversion of the abnormalities of MMP-2/9, TIMP-1/2, TNF-α, and ROS. But Dex had no influence on the hyperleptinemia and the upregulated leptin and its receptor in the myocardium during CHF. Conclusion: Dex improves CHF by inhibiting TNF-α, MMP-2, MMP-9, and ROS. Dex had no effects on upregulated leptin and its receptor expression and hyperleptinemia induced by CHF.

Keywords: leptin; chronic heart failure; matrix metalloproteinase 9; matrix metalloproteinase 2; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; tumor necrosis factor alpha; dexamethasone

Document Type: Research article

DOI: 10.1111/j.1745-7254.2007.00503.x

Affiliations: 1: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China 2: Department of Physiology, Wenzhou Medical College, Wenzhou 325003, China

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Improvement of chronic heart failure by dexamethasone is not associated with downregulation of leptin in rats