This study aimed to evaluate the role for
adenosine A2A receptors in the autoregulatory vasodilation to
hypotension in relation with cerebral blood flow (CBF) autoregulation in rat pial arteries. Changes in pial artery diameters were observed directly through a closed cranial window. Vasodilation induced by
adenosine was markedly suppressed by
ZM 241385 (1 micromol/l, A2A antagonist) and
alloxazine (1 micromol/l, A2B antagonist), but not by
8-cyclopentyltheophylline (
CPT, 1 micromol/l, A1 antagonist). CGS-21680-induced vasodilation was more strongly inhibited by
ZM 241385 (25.3-fold; P<0.05) than by
alloxazine. In contrast, 5'-N-ethylcarboxamido-adenosine (
NECA)-induced vasodilation was more prominently suppressed by
alloxazine (12.0-fold; P<0.001) than by
ZM 241385. The autoregulatory vasodilation in response to acute
hypotension of the pial arteries was significantly suppressed by
ZM 241385, but not by
CPT and
alloxazine. Consistent with this finding, the lower limit of CBF autoregulation significantly shifted to a higher blood pressure by 1 micromol/l of
ZM 241385 (53.0+/-3.9 mm Hg to 69.2+/-2.9 mm Hg, P<0.01) and 10 micromol/l of
glibenclamide (54.7+/-6.5 mm Hg to 77.9+/-4.2 mm Hg, P<0.001), but not by
CPT and
alloxazine. Thus, it is suggested that
adenosine-induced vasodilation of the rat pial artery is mediated via activation of
adenosine A2A and A2B receptors, but not by A1 subtype, and activation of
adenosine A2A receptor preferentially contributes to the autoregulatory vasodilation via activation of
ATP-sensitive K+ channels in response to
hypotension and maintenance of CBF autoregulation.