Adenosine receptors and vascular inflammation

Abstract

Epidemiological studies have shown a positive correlation between poor lung function and respiratory disorders like asthma and the development of adverse cardiovascular events. Increased adenosine (AD) levels are associated with lung inflammation which could lead to altered vascular responses and systemic inflammation. There is relatively little known about the cardiovascular effects of adenosine in a model of allergy. We have shown that A(1) adenosine receptors (AR) are involved in altered vascular responses and vascular inflammation in allergic mice. Allergic A(1)wild-type mice showed altered vascular reactivity, increased airway responsiveness and systemic inflammation. Our data suggests that A(1) AR is pro-inflammatory systemically in this model of asthma. There are also reports of the A(2B) receptor having anti-inflammatory effects in vascular stress; however its role in allergy with respect to vascular effects has not been fully explored. In this review, we have focused on the role of adenosine receptors in allergic asthma and the cardiovascular system and possible mechanism(s) of action.

Figure 1

Systemic inflammatory markers in plasma A) IL-5 B) IL-13 C) TNF-α in A₁WT non-allergic control (A₁WT CON), A₁WT allergic (A₁WT SEN), A₁WT allergic further challenged with adenosine (A₁WT SEN+AD) mice [40] *P<0.05 compared to WT CON; #P<0.05 compared to WT SEN

Figure 2

Plasma levels of IL-5 in A₁KO non-allergic control (A₁KO CON), A₁KO allergic (A₁KO SEN), A₁KO allergic further challenged with adenosine (A₁KO SEN+AD) mice (unpublished observation; IL-13 and TNF-α were not detected in A₁KO plasma)

Figure 3

Possible pathway for adenosine receptors as both pro- and anti-inflammatory effectors in vascular inflammation in asthma. “??” indicates unknown or possible mediators.