P2 purinoceptor-mediated dilations in the rat middle cerebral artery afterischemia-reperfusion

Endothelial-mediated dilations to selective P2Y(1) and P2Y(2) purinoceptor agonists [2-methylthioadenosine triphosphate (2MeS-ATP) and uridine 5'-trip hosphate (UTP), respectively] were evaluated in middle cerebral arteries (M CAs) of rats after 2 h of ischemia followed by 24 h of reperfusion (I/R). M CAs were harvested, pressurized to 85 mmHg, and luminally perfused. 2MeS-AT P, which dilates by the synthesis and release of nitric oxide (NO), had sig nificantly reduced maximum dilations following I/R. Reduced smooth muscle s ensitivity to NO may explain the reduced dilation to 2MeS-ATP. In contrast, the dilations elicited by UTP were potentiated in that the concentration o f agonist necessary to produce one-half of the maximum dilation was reduced by 75%. The potentiated dilation to UTP was the result of an endothelial f actor having all the characteristics of the endothelium-derived hyperpolari zing factor (EDHF). That is, it was neither NO nor a cyclooxygenase metabol ite, and its actions involved calcium-activated potassium channels and smoo th muscle hyperpolarization. We conclude that the effect of I/R on endothel ial-mediated dilations depends on the receptor system and the mechanism of dilation. Dilations elicited by 2MeS-ATP were attenuated, while dilations U TP were potentiated due to the upregulation of the EDHF mechanism.