Background and Purpose: Adenosine is a local mediator that regulates changes in the cardiovascular system via activation of four G protein-coupled receptors (A1, A2A, A2B, A3). Here we have investigated the effect of A2A and A2B-selective agonists on vasodilatation in three distinct vascular beds of the rat cardiovascular system. Experimental Approach: The regional haemodynamic effects of adenosine A2A and A2B selective agonists were investigated in conscious rats. Male Sprague-Dawley rats (350-450g) were chronically implanted with pulsed Doppler flow probes on the renal artery, mesenteric artery and the descending abdominal aorta. Cardiovascular responses were measured following intravenous infusion (3 min for each dose) of CGS 21680 (0.1, 0.3, 1 g.kg-1.min-1) or BAY 60-6583 (4,13.3, 40 g.kg-1.min-1) following pre-dosing with either SCH 58261 (0.1 or 1 mg.kg-1.min-1), PSB 1115 (10 mg.kg-1.min-1) or vehicle. Key Results: The A2A-selective agonist CGS 21680 produced a striking increase in heart rate (HR) and hindquarters vascular conductance (VC) that was accompanied by a significant decrease in mean arterial pressure (MAP) in conscious rats. In marked contrast, the A2B-selective agonist BAY 60-6583 significantly increased HR and VC in the renal and mesenteric vascular beds, but not in the hindquarters. Conclusions and Implications: Taken together, these data indicate that A2A and A2B receptors are regionally selective in their regulation of vascular tone. These results suggest that the development of A2B receptor agonists to induce vasodilatation in the kidney may provide a good therapeutic approach for the treatment of acute kidney injury.