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

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Abstract
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 A2A 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 A2A receptor subtype may be involved in this dilation response.