Am. J. Respir. Crit. Care Med., Volume 162, Number 1, July 2000, 310-315

Targeting the Angiotensin System in Posttransplant Airway Obliteration
The Antifibrotic Effect of Angiotensin Converting Enzyme Inhibition

ALEXANDRA A. MACLEAN, MINGYAO LIU, STEFAN FISCHER, MICHIHURA SUGA, and SHAF KESHAVJEE

Thoracic Surgery Research Laboratory, The Toronto General Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada

The angiotensin system plays a role in the pathogenesis of fibrotic diseases. We used a rat heterotopic tracheal transplant model of bronchiolitis obliterans (BO) to examine the role of angiotensin converting enzyme (ACE) in development of the fibroproliferative lesion of BO. Isograft and allograft tracheal transplants were performed. Allograft rats received either no treatment (control) or captopril (100 mg/kg/d) in their drinking water. The drug treatment given to the recipient rats was begun 5 days before transplantation, on postoperative Day 1, or on postoperative Day 5. The treatment was continued until postoperative Day 21, when tracheal specimens were harvested and subjected to histologic, immunohistologic, and morphometric analyses. We noted heavy staining for ACE in the obliterated portion of the tracheas of allograft control animals. This area was not present in nontransplanted or isograft tracheas. Captopril administration begun 5 d before transplantation and on postoperative Day 1 resulted in a significant attenuation in the percent airway obliteration (45% and 26%, respectively) as compared with that in control allografts (83%; p < 0.05). This study demonstrates the presence of ACE in the fibroproliferative lesion in a rat model of BO, and shows that inhibition of ACE can limit development of airway obliteration.

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