Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model

Abstract

Objectives: 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 mu m vs. 35.0 +/- 0.6 mu m; 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 mu m vs. 121.5 +/- 8.1 mu m; p = 0.005), improved compliance (163.6 +/- 55.9 mu l/cmH(2)O vs. 354.4 +/- 72.5 mu l/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. (C) 2010 Elsevier Ltd. All rights reserved.