title: Eprosartan improves cardiac performance, reduces cardiac hypertrophy and mortality and downregulates myocardial monocyte chemoattractant protein-1 and inflammation in hypertensive heart disease.
abstract: OBJECTIVE
  The purpose of this investigation was to determine whether angiotensin II receptor (AII1R) antagonism interferes with cardiac monocyte chemoattractant protein-1 (MCP-1) expression in hypertrophic cardiomyopathy and failure.
  
  
  METHODS
  We studied the effects of the AII1R antagonist eprosartan on MCP-1 expression, and on the recruitment of macrophages into the myocardium in a model of cardiac hypertrophy and morbidity/mortality.
  
  
  METHODS
  Stroke-prone spontaneously hypertensive rats fed a high-salt, high-fat diet (SFD) developed heart failure characterized by left ventricular (LV) hypertrophy/pathology and hypocontractility. These rats received either normal diet, SFD, or SFD with the daily administration of 30 mg/kg eprosartan for 28 weeks. LV function and wall thickness was assessed by echocardiography, MCP-1 expression was measured by TaqMan real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry, and macrophage infiltration into the LV was determined by microscopy.
  
  
  RESULTS
  Eprosartan reduced the rate of morbidity/mortality (P = 0.001), LV MCP-1 mRNA (P < 0.05) and protein expression (P < 0.01), and LV macrophage infiltration (P < 0.01), while preserving ventricular function (P < 0.05). Eprosartan also produced a moderate (16%; P < 0.05) decrease in blood pressure.
  
  
  CONCLUSIONS
  These data demonstrate that AII1R antagonism in an animal model of hypertensive heart disease reduces MCP-1 expression in the myocardium that results in reduced macrophage recruitment. These effects parallel the preservation of LV systolic function and the reduction in cardiac remodeling/disease progression and reduced morbidity/mortality. Suppression of MCP-1 expression might explain in part the beneficial effects of AII1R antagonism in this model.
authors.affiliation: Medizinische Poliklinik, Department of Cardiology, University of Wuerzburg, Germany. t.behr@medizin.uni-wuerzburg.de
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Behr
authors.forename: Robert N
authors.initials: RN
authors.lastname: Willette
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coatney
authors.forename: Marinela
authors.initials: M
authors.lastname: Berova
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Angermann
authors.forename: Karen
authors.initials: K
authors.lastname: Anderson
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Sackner-Bernstein
authors.forename: Frank C
authors.initials: FC
authors.lastname: Barone
mesh_terms: D000179:Acrylates / Q000008:administration & dosage*; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D007093:Imidazoles / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D013876:Thiophenes; D014463:Ultrasonography; D014657:Vasculitis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality
chemical_list: D000179:Acrylates; D000959:Antihypertensive Agents; D018932:Chemokine CCL2; D007093:Imidazoles; D012333:RNA, Messenger; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan