title: Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model.
abstract: OBJECTIVE
  COPD with emphysema causes marked neurohumoral activation. Angiotensin II receptors are highly expressed within the lung and interfere with mechanisms involved in the progression of emphysema. This study examined the effects of an angiotensin II receptor blocker (ARB) on pulmonary and systemic manifestations of emphysema in a mouse model.
  
  
  METHODS
  Female NMRI mice received five intratracheal instillations of porcine pancreatic elastase (emphysema; n = 11) or phosphate-buffered saline (PBS; n = 4). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, and lung biomechanics by compliance. Following emphysema induction, 6 mice were treated with the ARB irbesartan for 8 weeks, while 5 mice receiving standard food served as controls.
  
  
  RESULTS
  Following emphysema induction, mean linear intercept was higher in elastase-treated than in PBS-treated lungs (103.0 ± 6.2 μm vs. 35.0 ± 0.6 μm; p = 0.043) while running distance was shorter in emphysema mice (418.6 ± 83.5 m vs. 906.6 ± 244.6 m, p = 0.028). Irbesartan-treated emphysema mice showed a lower mean linear intercept (90.8 ± 3.8 μm vs. 121.5 ± 8.1 μm; p = 0.005), improved compliance (163.6 ± 55.9 μl/cmH(2)O vs. 354.4 ± 72.5 μl/cmH(2)O; p = 0.063) and greater running distance (p ANOVA = 0.015) compared to emphysema mice receiving standard food.
  
  
  CONCLUSIONS
  The ARB irbesartan elicits encouraging beneficial effects on emphysema severity, lung biomechanics and exercise capacity in an emphysema mouse model. These findings might help to understand the corresponding positive effects of angiotensin II receptor blockade noticed in patients with COPD.
authors.affiliation: Department of Cardiology and Pneumology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Raupach
authors.forename: Lars
authors.initials: L
authors.lastname: Lüthje
authors.forename: Harald
authors.initials: H
authors.lastname: Kögler
authors.forename: Christian
authors.initials: C
authors.lastname: Duve
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Stefan
authors.initials: S
authors.lastname: Andreas
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D017079:Exercise Tolerance; D005260:Female; D000077405:Irbesartan; D051379:Mice; D010196:Pancreatic Elastase; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D010196:Pancreatic Elastase; D000077405:Irbesartan