Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salt hypertensive rats

被引:84
作者
Kagitani, S [1 ]
Ueno, H [1 ]
Hirade, S [1 ]
Takahashi, T [1 ]
Takata, M [1 ]
Inoue, H [1 ]
机构
[1] Toyama Med & Pharmaceut Univ, Dept Internal Med 2, Toyama 9300194, Japan
关键词
deoxycorticosterone-acetate salt hypertensive rats; myocardial fibrosis; monocyte/macrophage; transforming growth factor-beta(1); tranilast;
D O I
10.1097/00004872-200405000-00024
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective In order to study the association between myocardial fibrosis and inflammatory cell infiltration in the hypertensive heart, we investigated whether N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast), an anti-inflammatory drug, would suppress myocardial fibrosis via inhibition of inflammatory cell infiltration in deoxycorticosterone-acetate (DOCA) hypertensive rats. Methods Sprague-Dawley rats treated with DOCA combined with the addition of 1% NaCl and 0.2% KCl in the drinking water after left nephrectomy were given tranilast (100 mg/kg per day, n = 15) or vehicle (n = 15) for up to 4 weeks. Systolic blood pressure (SBP), amount of myocardial interstitial fibrosis, perivascular fibrosis and type I and III collagen, and mRNA expression of procollagen I (PI) and procollagen III (PIII), transforming growth factor (TGF)-beta(1), type-1 plasminogen activator inhibitor (PAI-1), monocyte chemoattractant protein (MCP)1 and interleukin (IL)-6 were determined. Results SBP was increased significantly 2 weeks after treatment with DOCA and salt. Myocardial interstitial fibrosis, perivascular fibrosis and collagen accumulation increased significantly 4 weeks after the treatment. Two weeks after the treatment with DOCA and salt, m RNA expression of PI and PIII, TGF-beta(1), PAI-1, MCP-1 and IL-6 increased significantly. Although the SBP was similar in animals treated with tranilast or vehicle, monocyte/macrophage infiltration was suppressed, mRNA expression of TGF-beta(1), PAI-1, MCP-1, IL-6, PI and PIII was attenuated, and myocardial fibrosis and collagen accumulation were suppressed in hypertensive animals receiving tranilast. Conclusion Myocardial fibrosis seen in DOCA/salt hypertensive rats might be associated with the inflammation/wound healing response. Tranilast suppresses both infiltration of monocytes/macrophages and myocardial fibrosis. (C) 2004 Lippincott Williams Wilkins.
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页码:1007 / 1015
页数:9
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