Purpose: Previous studies have shown that adenosine induces relaxation of isolated retinal arterioles mediated by the A2A receptor, but the contributions to tone regulation of adenosine receptors located both in and around the vascular wall have not been studied in detail.

Methods: Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was recorded after addition of antagonists to the adenosine A1, A2A, A2B, and A3 receptors, followed by removal of the perivascular retinal tissue and repetition of the experiments. Additionally, these responses were studied in concentration-response experiments using specific agonists.

Results: Adenosine induced a significant concentration-dependent relaxation at high concentrations that was independent of the perivascular retinal tissue and could be antagonized by the nonspecific adenosine receptor antagonist 8-PSPT. The selective A2A receptor antagonist SCH 58261 and the A2B receptor antagonist MRS 1754 significantly antagonized the relaxing effect of adenosine. Conversely, the selective A1 receptor antagonist KW-3902 and the A3 receptor antagonist MRS 1523 significantly increased the relaxing effect of adenosine, and the corresponding agonists contracted retinal arterioles at intermediate concentrations. The contracting effect of the A1 receptor agonist but not the A3 receptor antagonist depended on the presence of perivascular retinal tissue.

Conclusions: Adenosine has complex effects on retinal vascular tone elicited both from the vascular wall and from the perivascular retina and with receptors mediating contraction at intermediate concentrations and relaxation at high concentration.