Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex

We tested the hypothesis that adenosine (Ado) mediates glutamate-induced vasodilation in the cerebral cortex by monitoring pial arteriole diameter in chloralose-anesthetized rats equipped with closed cranial windows. Topical application of 100 μM glutamate and 100 μM N-methyl-D-aspartate (NMDA) dilated pial arterioles (baseline diameter 25 ± 2 μm) by 17 ± 1% and 18 ± 4%, respectively. Coapplication of the nonselective Ado receptor antagonist theophylline (Theo; 10 μM) significantly reduced glutamate- and NMDA-induced vasodilation to 4 ± 2% (P < 0.01) and 6 ± 2% (P < 0.05), whereas the Ado A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 μM) had no effect. Moreover, application of the Ado A_2A receptor-selective antagonist 4-{2-[7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a)(1,3,5)-triazin-5- ylamino]ethyl}phenol (ZM-241385), either by superfusion (0.1 μM, 1 μM) or intravenously (1 mg/kg), significantly inhibited the pial arteriole dilation response to glutamate. Neither Theo nor ZM-241385 affected vascular reactivity to mild hypercapnia induced by 5% CO₂ inhalation. These results suggest that Ado contributes to the dilation of rat cerebral arterioles induced by exogenous glutamate, and that the Ado A_2A receptor subtype may be involved in this dilation response.