title: Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salt hypertensive rats.
abstract: 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)-beta1, 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-beta1, 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-beta1, PAI-1, MCP-1, IL-6, PI and PIII was attenuated, and myocardial fibrosis and collagen accumulation were suppressed in hypertensive animals receiving tranilast.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kagitani
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirade
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Takata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D006332:Cardiomegaly / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D003900:Desoxycorticosterone / Q000494:pharmacology; D005355:Fibrosis; D006973:Hypertension / Q000150:complications*; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology; D009206:Myocardium / Q000473:pathology; D009392:Nephrectomy; D009929:Organ Size; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D024042:Collagen Type I; D024061:Collagen Type III; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates; D003900:Desoxycorticosterone; C012293:tranilast