Losartan does not inhibit cigarette smoke-induced lung inflammation in mice

R. Vlahos,S. L. Passey,M. L. Hepworth,H. J. Seow

doi:10.1038/s41598-019-51504-2

R. Vlahos, S. L. Passey + Show 2 more

Open Access

https://doi.org/10.1038/s41598-019-51504-2

Copy DOI

Journal: Scientific Reports	Publication Date: Oct 21, 2019
Citations: 7	License type: open-access

Affiliation: RMIT University

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.

Highlights

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
We examined whether losartan, an angiotensin-II AT1 receptor antagonist widely used to treat hypertension associated with cardiovascular disease, would significantly reduce lung inflammation in mice chronically exposed to cigarette smoke (CS)
COPD consists of a persistent lung inflammation that leads to reduced airflow and systemic inflammation that leads to comorbidities including cardiovascular disease

Summary

Introduction

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. 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. 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. The number of neutrophils in the bronchoalveolar lavage fluid (BALF) and lung tissue of COPD patients in increased[2,3]. Epidemiological studies have suggested that angiotensin converting enzyme (ACE) inhibitors which are used to treat hypertension and cardiac failure (common comorbidities of COPD), may benefit COPD, by reducing mortality and exacerbations[18,19,20,21]. Randomized clinical trials of ARBs are underway to evaluate their effect on the progression of emphysema in COPD (https://clinicaltrials.gov/ct2/show/NCT02696564)

Objectives

Methods

Results

Conclusion