ENDOTHELIAL-MEDIATED DILATIONS OF RAT MIDDLE CEREBRAL-ARTERIES BY ATPAND ADP

The hypothesis that ATP and ADP produce dilations of rat middle cerebr al arteries (MCAs) by different mechanisms was tested. Vessel diameter s were measured from pressurized, perfused MCAs after application of d ifferent agonists. The luminal administration of ATP and ADP elicited concentration-dependent dilations (35% maximum). Removal of endotheliu m abolished the dilation to intraluminal ATP and attenuated the dilati on to intraluminal ADP. The dilations to ATP were abolished with N-ome ga-nitro-L-arginine methyl ester (L-NAME; 10 mu M), a nitric oxide syn thase inhibitor, at ATP concentrations of 1 mu M and below. However, a t concentrations of 10 mu M. ATP and above, L-NAME had no effect on th e response. The dilations to ADP were attenuated by L-NAME to the same degree as removal of endothelium. The mechanism for dilation by ATP w as identical to that of UTP, a selective P-2u purinoceptor agonist. Th e mechanism of dilation by ADP was similar to that of 2-methylthioaden osine 5'triphosphate, a selective P-2y purinoceptor agonist. We conclu de that ATP and ADP elicit dilations of rat MCA by different mechanism s. ATP and ADP likely stimulate P-2u and P-2y purinoceptors, respectiv ely.