Adenosine-induced relaxation of cultured bovine retinal pericytes.

PURPOSE To investigate the effect of adenosine on the contractile tone of cultured bovine retinal pericytes. METHODS Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes on the silicone surface on which the cells were grown. RESULTS Adenosine at 10(-9) M had no effect. In the range of 10(-8) to 10(-4) M, adenosine caused relaxation of pericytes in a concentration-dependent manner. Complete relaxation was induced by 10(-5) M to 10(-4) M adenosine. The concentration of adenosine that produced 50% relaxation was 3 x 10(-7) M. At all concentrations, relaxation began within 1 minute, reached the maximum within 5 to 10 minutes, and persisted for at least 30 minutes. After a washout of 3 x 10(-7) M adenosine, the reduced contractile tone recovered to the original level in 10 minutes. The adenosine-induced relaxation (3 x 10(-7) M) was completely abolished in the presence of 8-phenyl theophylline (10(-5) M), a nonselective adenosine receptor antagonist. The selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-6) M did not reduce the effect of adenosine (3 x 10(-7) M). Conversely, the selective A2 receptor antagonist CP-66,713 at 10(-8) M partially inhibited (and at 10(-7) M, completely inhibited) the relaxation induced by adenosine (3 x 10(-7) M). The adenosine receptor antagonists-8-phenyl theophylline (10(-5) M), DPCPX (10(-6) M), and CP-66,713 (10(-7) M) by themselves had no effect on the contractile tone of pericytes. CONCLUSIONS Adenosine causes relaxation of pericytes through the activation of the adenosine A2 receptor. Adenosine, which accumulates under ischemic conditions, may help to regulate local capillary blood flow.