Functional characterization of coronary vascular adenosine receptors in the mouse

Coronary responses to adenosine agonists were assessed in perfused mouse and rat hearts. The roles of nitric oxide (NO) and ATP‐dependent K + channels (K ATP ) were studied in the mouse. Resting coronary resistance was lower in mouse vs rat, as was minimal resistance (2.2±0.1 vs 3.8±0.2 mmHg ml −1  min −1  g −1 ). Peak hyperaemic flow after 20–60 s occlusion was greater in mouse. Adenosine agonists induced coronary dilation in mouse, with pEC 50 s of 9.4±0.1 for 2‐[p‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethyl carboxamidoadenosine (CGS21680, A 2A ‐selective agonist), 9.3±0.1 for 5′‐N‐ethylcarboxamidoadenosine (NECA, A 1 /A 2 agonist), 8.4±0.1 for 2‐chloroadenosine (A 1 /A 2 agonist), 7.7±0.1 for N 6 ‐(R)‐(phenylisopropyl)adenosine (R‐PIA, A 1 /A 2B selective), and 6.8±0.2 for adenosine. The potency order (CGS21680=NECA>2‐chloroadenosine>R‐PIA>adenosine) supports A 2A adenosine receptor‐mediated dilation in mouse coronary vessels. 0.2–2 μ M of the A 2B ‐selective antagonist alloxazine failed to alter CGS21680 or 2‐chloroadenosine responses. pEC 50 s in rat were 6.7±0.2 for CGS21680, 7.3±0.1 for NECA, 7.6±0.1 for 2‐chloroadenosine, 7.2±0.1 for R‐PIA, and 6.2±0.1 for adenosine (2‐chloroadenosine>NECA=R‐PIA>CGS21680> adenosine), supporting an A 2B adenosine receptor response. NO‐synthase antagonism with 50 μ M N G ‐nitro L ‐arginine ( L ‐NOARG) increased resistance by ∼25%, and inhibited responses to CGS21680 (pEC 50 =9.0±0.1), 2‐chloroadenosine (pEC 50 =7.3±0.2) and endothelial‐dependent ADP, but not sodium nitroprusside (SNP). K ATP channel blockade with 5 μ M glibenclamide increased resistance by ∼80% and inhibited responses to CGS21680 in control (pEC 50 =8.3±0.1) and L ‐NOARG‐treated hearts (pEC 50 =7.3±0.1), and to 2‐chloroadenosine in control (pEC 50 =6.7±0.1) and L ‐NOARG‐treated hearts (pEC 50 =5.9±0.2). In summary, mouse coronary vessels are more sensitive to adenosine than rat vessels. A 2A adenosine receptors mediate dilation in mouse coronary vessels vs A 2B receptors in rat. Responses in the mouse involve a sensitive NO‐dependent response and K ATP ‐dependent dilation.British Journal of Pharmacology (2001) 133 , 1063–1072; doi: 10.1038/sj.bjp.0704170