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

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 antiinflammatory 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% KCI 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 (Pill), transforming growth factor (TGF)-β 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, mRNA expression of PI and PIII, TGF-β 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-β 1 , PAI-1, MCP-1, IL-6, PI and Pill 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.