title: Lung structural remodeling and pulmonary hypertension after myocardial infarction: complete reversal with irbesartan.
abstract: OBJECTIVE
  The severity of pulmonary hypertension associated with heart failure carries a poor prognosis. The lungs are very sensitive to the constrictive and proliferative effects of angiotensin-II and could represent a preferential target for this peptide.
  
  
  METHODS
  Rats with large myocardial infarcts or sham surgery received the angiotensin-II receptor antagonist irbesartan (40 mg/kg/day) or vehicle for 2 or 8 weeks (n=5 to 8 for each group). Hemodynamic and morphometric measurements were obtained followed by immunohistochemistry, immunofluorescence analysis and electron microscopic characterization of lung sections.
  
  
  RESULTS
  The infarct groups developed progressive pulmonary hypertension and right ventricular hypertrophy with elevated left ventricular filling pressures (all P<0.01). Despite similar infarct size, filling pressures were lower (P<0.01) while pulmonary hypertension and right ventricular hypertrophy were completely normalized by irbesartan. Isolated lungs pressure-flow relationships were identical at 2 weeks. At 8 weeks it was steepest and shifted upward in the infarct group (P<0.001), and completely normalized by irbesartan. Lung weight doubled after infarct with no evidence of pulmonary edema and was also normalized by irbesartan. Important lungs structural remodeling evidenced by collagen and reticulin deposition, thickening of the alveolar septa and proliferation of cells with ultrastructural characteristics of myofibroblasts (pericytes) were identified after infarct.
  
  
  CONCLUSIONS
  After large myocardial infarct there is important pulmonary structural remodeling in which myofibroblasts (pericytes) proliferation may play an important role. This initially protective mechanism against high filling pressures could eventually contribute to the development of pulmonary hypertension and right ventricular hypertrophy. Future studies are needed to determine if angiotensin-II directly modulates pulmonary remodeling after myocardial infarct.
authors.affiliation: Research Center, Montreal Heart Institute and University of Montreal, Quebec, Montreal, Canada
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
authors.forename: Tack-Ki
authors.initials: TK
authors.lastname: Leung
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Dupuis
mesh_terms: D000199:Actins / Q000032:analysis; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003893:Desmin / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D000077405:Irbesartan; D017493:Leukocyte Common Antigens / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D032342:Muscle Cells / Q000473:pathology / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000627:therapeutic use*; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D057912:Angiotensin II Type 2 Receptor Blockers; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D003893:Desmin; D005169:Factor VIII; D000077405:Irbesartan; D017493:Leukocyte Common Antigens; D013777:Tetrazoles; C067980:CD68 antigen, human; D000097382:CD68 Molecule