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Published on: February 21, 2011
Losartan does not inhibit cigarette smoke-induced lung inflammation in mice
M L Hepworth1, S L Passey1, H J Seow1
1School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
Insights
Losartan did not reduce lung inflammation in mice exposed to cigarette smoke (CS). While it lowered IL-6 mRNA and Angiotensin-II receptor expression, it failed to inhibit CS-induced cellularity in bronchoalveolar lavage fluid.
Area of Science:
- Pulmonary Medicine
- Cardiovascular Research
- Pharmacology
Background:
- Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease primarily caused by cigarette smoking (CS), leading to lung inflammation and irreversible airflow limitation.
- Cardiovascular comorbidities are prevalent in COPD patients, contributing to significant mortality, yet current treatments offer limited benefits.
- Concurrent therapeutic strategies targeting both lung and cardiovascular systems are needed for COPD management.
Purpose of the Study:
- To investigate the protective effects of losartan, an angiotensin-II AT1a receptor antagonist, against cigarette smoke-induced lung inflammation in a mouse model.
- To assess whether losartan can mitigate the inflammatory and cellular responses in the lungs following chronic CS exposure.
Main Methods:
- Male BALB/c mice were exposed to cigarette smoke (CS) for 8 weeks.
- Mice were treated daily with either losartan (30 mg/kg) or a vehicle control.
- Bronchoalveolar lavage fluid (BALF) was analyzed for cellularity, and whole lung tissue was assessed for cytokine, chemokine, and protease mRNA expression.
Main Results:
- CS exposure significantly increased BALF total cells, macrophages, and neutrophils.
- CS induced elevated mRNA expression of IL-6, TNF-α, CXCL-1, IL-17A, and MMP12 in lung tissue.
- Losartan treatment only reduced CS-induced IL-6 mRNA expression and did not significantly alter BALF cellularity.
- Angiotensin-II receptor expression was found to be reduced in lung tissue from CS-exposed mice.
Conclusions:
- Losartan did not effectively inhibit cigarette smoke-induced lung inflammation or cellularity in bronchoalveolar lavage fluid.
- While losartan reduced IL-6 mRNA and Angiotensin-II receptor expression, its overall efficacy in mitigating CS-induced lung pathology was limited in this model.
- Further research is needed to explore alternative or combination therapies for COPD and its cardiovascular comorbidities.
Abstract:
Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease largely caused by cigarette smoking (CS) and is characterized by lung inflammation and airflow limitation that is not fully reversible. Approximately 50% of people with COPD die of a cardiovascular comorbidity and current pharmacological strategies provide little benefit. Therefore, drugs that target the lung and the cardiovascular system concurrently may be an advantageous therapeutic strategy. The aim of this study was to see whether losartan, an angiotensin-II AT1a receptor antagonist widely used to treat hypertension associated with cardiovascular disease, protects against CS-induced lung inflammation in mice. Male BALB/c mice were exposed to CS for 8 weeks and treated with either losartan (30 mg/kg) or vehicle daily. Mice were euthanized and bronchoalveolar lavage fluid (BALF) inflammation, and whole lung cytokine, chemokine and protease mRNA expression assessed. CS caused significant increases in BALF total cells, macrophages, neutrophils and whole lung IL-6, TNF-α, CXCL-1, IL-17A and MMP12 mRNA expression compared to sham-exposed mice. However, losartan only reduced CS-induced increases in IL-6 mRNA expression. Angiotensin-II receptor expression was reduced in lung tissue from CS-exposed mice. In conclusion, losartan did not inhibit CS-induced BALF cellularity despite reducing whole lung IL-6 mRNA and Ang-II receptor expression.
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