Relative responses to luminal and adventitial adenosine in perfused arteries

Responses to luminal and adventitial adenosine were compared in perfused rabbit central ear arteries. Perfused arteries precontracted with 0.5 μM norepinephrine relaxed dose dependently but asymmetrically to luminal and adventitial adenosine. Arteries were more responsive to luminal adenosine in the 0.1- to 1.0-μM range, but they were more responsive to adventitial adenosine at doses >10 μM. Alternatively, 2-chloroadenosine, a metabolically stable and poorly transported analogue, was equipotent when applied luminally or adventitially. Endothelial damage reduced sensitivity and response asymmetry to luminal and adventitial adenosine. This was consistent with reduced responses to adenosine in luminally rubbed arterial ring segments. Transport inhibition (10 μM dipyridamole) enhanced arterial reactivity to luminal and adventitial adenosine and reduced response asymmetry but was without effect on responses to 2-chloroadenosine. A comparison of the inhibitory effectiveness of adventitial and luminal 8-phenyltheophylline revealed that adventitial antagonist was approximately threefold more effective in inhibiting responses to adventitial adenosine than luminal antagonist (P < 0.05). This 'side-dependent' difference was reduced by prolonged antagonist incubation or endothelial removal. The data indicate that adenosine relaxes ear arteries by activation of smooth muscle [half- maximum effective concentration (ED₅₀) ~ 11 μM] and endothelial (ED₅₀ ~ 2 μM) receptors. Nevertheless, a sensitive endothelial-dependent response does not consistently enhance responses to luminal adenosine in perfused arteries. This appears to be attributable to relative differences in the smooth muscle and endothelium-dependent components of the dilator response and transvascular concentration gradients for luminally and adventitially applied adenosine. A transendothelial diffusion barrier also reduces the ability of luminally applied antagonists to inhibit responses to adventitial adenosine.