Endothelial-mediated dilations of rat middle cerebral arteries by ATP and ADP

The hypothesis that ATP and ADP produce dilations of rat middle cerebral arteries (MCAs) by different mechanisms was tested. Vessel diameters were measured from pressurized, perfused MCAs after application of different agonists. The luminal administration of ATP and ADP elicited concentration-dependent dilations (35% maximum). Removal of endothelium abolished the dilation to intraluminal ATP and attenuated the dilation to intraluminal ADP. The dilations to ATP were abolished with N-omega-nitro-L-arginine methyl ester (L-NAME; 10 mu M), a nitric oxide synthase inhibitor, at ATP concentrations of 1 mu M and below. However, at concentrations of 10 mu M. ATP and above, L-NAME had no effect on the response. The dilations to ADP were attenuated by L-NAME to the same degree as removal of endothelium. The mechanism for dilation by ATP was identical to that of UTP, a selective P-2u purinoceptor agonist. The mechanism of dilation by ADP was similar to that of 2-methylthioadenosine 5'triphosphate, a selective P-2y purinoceptor agonist. We conclude that ATP and ADP elicit dilations of rat MCA by different mechanisms. ATP and ADP likely stimulate P-2u and P-2y purinoceptors, respectively.