Angiotensin II type 1 receptor blocker inhibits pulmonary injury.
OBJECTIVE
Pulmonary damage and fibrosis may be the result of diverse forms of injury and there is an association between pulmonary diseases and cardiovascular events. The purpose of this study was to evaluate the effects of an angiotensin II type 1 receptor blocker, valsartan, on systemic, cellular, and fibrotic consequences of pulmonary injury induced by the anti-neoplastic antibiotic, bleomycin.


METHODS
Sprague Dawly rats were used in the classical bleomycin model of pulmonary fibrosis. Bleomycin (1 unit, n = 7) was administered intra-tracheally to induce lung injury. Valsartan (0.66 mg) was given either concomitantly (n = 9) or for two days prior to bleomycin (n = 8). A control group (n = 6) was given normal saline.


RESULTS
Valsartan-treated animals showed abrogation of weight loss, suppression of release of total and active transforming growth factor beta-1 (TGF-beta1), and diminished connective tissue synthesis. In an explant, lung tissue culture model devoid of alveolar macrophages (saline control, n = 3; bleomycin, n = 6; bleomycin plus valsartan, n = 12), both total and active TGF-beta1 were suppressed in the valsartan-treated cohort.


CONCLUSIONS
Valsartan, known to have cardio-protective properties, was shown to be protective of bleomycin-induced pulmonary injury. Thus, ARBs may be beneficial in both cardiac and pulmonary diseases.
Mancini
G B John
GB
Department of Medicine, Division of Cardiology, University of British Columbia and Vancouver Coastal Research Institute, Vancouver, Canada. mancini@interchange.ubc.ca
Khalil
Nasreen
N
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D000964:Antimetabolites, Antineoplastic; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D055513:Connective Tissue Growth Factor; D000068756:Valsartan; D003094:Collagen; D014633:Valine