Objective

Adenosine is a reactive metabolite which mediates protection against cellular stresses, such as inflammation and hypoxia [1]. In metabolically compromised tissues, adenosine A₁ and A₂ receptors help to optimise ATP utilisation and oxygen supply through arteriolar vasodilatation and regulation of myocardial contractility [2]. Here, we investigated the effects of adenosine or a specific A_2A agonist, CGS21680 on regional haemodynamics in the presence or absence of an A_2A-specific antagonist, SCH58261. As described previously [3], male, Sprague-Dawley rats were implanted with miniature pulsed Doppler flow probes (sutured around the renal and mesenteric arteries and the descending abdominal aorta) for the measurement of vascular conductance. Subsequently, intra-arterial and intra-venous catheters were implanted for measurement of heart rate (HR) and mean arterial pressure (MAP), and drug administration, respectively. All procedures were carried out with approval of the University of Nottingham Animal Welfare Ethical Review Board, under Home Office Project and Personal License Authority. All compounds were prepared in PEG (5% propylene glycol, 2% Tween, 0.9% saline) or saline. Agonists were administered in the presence or absence of SCH58261 or vehicle (0.1 or 1.0 mg/kg; given as a bolus of 0.1ml). For example, a bolus injection of SCH58261 or vehicle was administered following a baseline period. Approximately 10 mins after this initial injection, CGS21680 was administered as 3 min infusions of 0.1, 0.3 and 1 μg/kg/min administered over a total of 9 min at an infusion rate of 0.1ml/min. CGS21680 produced tachycardic and depressor effects, which were associated with renal and hindlimb vasodilatations. There was little effect in the mesenteric vascular bed. Responses were mostly antagonised by SCH58261 at 1.0 mg/kg. Responses to adenosine and other modulators of adenosine receptors (e.g. VCP746) will also be presented. In conclusion, these data suggest that individual A_2A-receptor agonists produce differential effects on vascular conductance in specific vascular beds, which may be due to ligand interactions with the A₁- or A_2B-receptors.