Objective and design: To determine whether exposure to E. coli lipopolysaccharide (LPS) modulates adenosine A(1) receptor-induced increase in plasma exudation from the intact hamster cheek pouch microcirculation.
Methods and results: Using intravital microscopy, we found that suffusion of R(-)-N(6)-(2-phenylisopropyl)-adenosine (R(-)-PIA) (1.0 and 10.0 nM), a selective adenosine A(1) receptor agonist, onto the intact cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein thioisocyanate-dextran (mol mass, 70 kDa) from post-capillary venules (p < 0.05). These responses were significantly attenuated by pre-treatment of hamsters with LPS (p < 0.05). By contrast, LPS had no significant effects on CGS-21680-, a selective adenosine A(2A) receptor agonist, bradykinin- and substance P-induced increases in plasma exudation from the cheek pouch.
Conclusion: These data indicate that LPS attenuates adenosine A(1) receptor-induced increase in plasma exudation in vivo in a specific fashion. We suggest that this phenomenon represents an endogenous anti-inflammatory cue to avoid excessive inflammation during Gram-negative bacterial infections.