Abstract
Recent studies have shown that asthma induces cardiovascular (CV) complications with no clear cause. We hypothesize that chronic lung inflammation leads to systemic inflammation that causes adverse CV effects. This study was conducted to examine the effect of adenosine (AD) on vascular reactivity and inflammatory mediators in plasma and BAL in our mouse model of allergic asthma. Balb/C mice were divided into 4 groups: Control (C), Control +AD (C+AD), allergen challenge (S), allergen challenge +AD (S+AD). Mice were sensitized i.p. on days 1, 6 with ragweed followed by allergen challenges on days 11–13. C+AD and S+AD received a single aerosolized challenge of AD (6mg/ml) on day 14. S had significantly impaired (p<0.05) aortic relaxation to AD and lowered response to ACh (p<0.05). Relaxation was further impaired in S+AD. Tissues were also incubated with A1 blocker DPCPX (10−5 M) prior to obtaining AD dose response. S and S+AD showed relaxation similar to control (25–30%). Plasma levels of IL‐1β, 7, 9, 13, 15, MCP‐1, MIP‐1α, CRP, TNF‐α were significantly elevated in S+AD (p<0.05). IL‐5, 6, 17 were elevated significantly in S and S+AD (p<0.05). BAL analysis showed highest levels of IL‐2, 4, 5 and TNF‐α in S+AD (p<0.05). In conclusion, allergic mice had altered peripheral vascular reactivity and systemic inflammation with inhaled AD exacerbating the A1 receptor‐mediated effects on vascular tone.
Supported by HL027339.