Adenosine clearly regulates coronary blood flow (CBF); however, contributions of specific adenosine receptor (AR) subtypes (A 1 , A 2A , A 2B , A 3 ) to CBF in swine have not been determined. ARs generally decrease (A 1 , A 3 ) or increase (A 2A , A 2B ) cyclic adenosine monophosphate, a major mediator of vasodilation. We hypothesized that A 1 antagonism potentiates coronary vasodilation and coronary stent deployment in dyslipidemic Ossabaw swine elicits impaired vasodilation to adenosine that is associated with increased A 1 /A 2A expression. The left main coronary artery was accessed with a guiding catheter allowing intracoronary infusions. After placement of a flow wire into the left circumflex coronary artery the responses to bolus infusions of adenosine were obtained. Steady-state infusion of AR-specific agents was achieved by using a small catheter fed over the flow wire in control pigs. CBF was increased by the A 2 -nonselective agonist 2-phenylaminoadenosine (CV1808) in a dose-dependent manner. Baseline CBF was increased by the highly A 1 -selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not changed by other AR-specific agents. The nonselective A 2 antagonist 3,7-dimethyl-1-propargylxanthine and A 2A -selective antagonist 4-(2-[7-amino-2-(2-furyl) [1,2,4] triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) abolished adenosine-induced CBF, whereas A 2B and A 3 antagonism had no effect. Dyslipidemia and stenting decreased adenosine-induced CBF ϳ70%, whereas A 1 , A 2A , and A 2B mRNA were up-regulated in dyslipidemic versus control Ͼ5-fold and there was no change in the ratio of A 1 /A 2A protein in microvessels distal to the stent. In control Ossabaw swine A 1 antagonism by DPCPX positively regulated basal CBF. Impaired adenosine-induced CBF after stenting in dyslipidemia is most likely caused by the altered balance between A 1 and A 2A signaling, not receptor expression.