Chronic CS exposure causes endothelial dysfunction in mouse thoracic aorta
The effect of chronic CS exposure on vascular function was examined to establish if the enhanced oxidative stress and inflammation arising from smoking has detrimental effects on blood vessel function in vivo . ACh (10-8 to 10-5 M) caused an ~90% maximal relaxation (Rmax) of U46619-precontracted thoracic aorta obtained from sham-exposed mice (Figure 1A). However, in thoracic aorta taken from CS-exposed mice, endothelial-dependent vasodilatory responses were significantly impaired (~40% Rmax, p<0.05 ) demonstrating that chronic CS exposure causes endothelial dysfunction. Sodium nitroprusside (10-8 to 10-5M) caused an ~90-95% maximal relaxation of aortae taken from both sham and CS-exposed mice with no statistically significant difference observed between groups (Figure 1B), suggesting CS exposure has no effect on vascular smooth muscle function.
CS exposure drives pulmonary immune cell infiltration, pro-inflammatory and oxidative stress gene expression
CS exposure caused a significant increase in the total number of immune cells infiltrating the lungs when compared to sham-exposed control mice (Figure 2A,p<0.05 ). This increase in total cell number was attributed to a significant increase in macrophages, neutrophils and lymphocytes) (Figures 2B, C & D, p<0.05 ).
To better understand the mechanism(s) underlying the increased BALF inflammation, the pulmonary expression of both pro-inflammatory and oxidative stress genes was examined. CS exposure caused a significant increase in mRNA expression of the pro-inflammatory cytokines TNF-α (2.2-fold) and IL-6 (4.7-fold), as well as the key oxidative stress enzyme NOX-2 (1.5-fold; Figures 2, F & G, p<0.05 ).