Functional characterization of coronary vascular adenosine receptors in the mouse

1 Coronary responses to adenosine agonists were assessed in perfused mouse and rat hearts. The roles of nitric oxide (NO) and ATP-dependent K+ channel s (K-ATP) were studied in the mouse. 2 Resting coronary resistance was lower in mouse rs rat, as was minimal res istance (2.2 +/-0.1 vs 3.8 +/-0.2 mmHg ml(-1) min(-1) g(-1)). Peak hyperaem ic flow after 20-60 s occlusion was greater in mouse. 3 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 carboxamido adenosine (CGS21680, A(2A)-selective agonist), 9.3 +/-0.1 for 5 ' -N-ethylc arboxamidoadenosine (NECA, A(1)/A(2) agonist), 8.4 +/-0.1 for 2-chloroadeno sine (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 o rder (CGS21680=NECA >2-chloroadenosine >R-PIA > adenosine) supports A(2A) a denosine receptor-mediated dilation in mouse coronary vessels. 0.2-2 muM of the A(2B)-selective antagonist alloxazine failed to alter CGS21680 or 2-ch loroadenosine responses. 4 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 adenos ine (2-chloroadenosine > NECA = R-PIA > CGS21680 > adenosine), supporting a n A(2B) adenosine receptor response. 5 NO-synthase antagonism with 50 muM N-G-nitro-L-arginine (L-NOARG) increas ed resistance by similar to 25%, and inhibited responses to CGS21680 (pEC(5 0)=9.0 +/-0.1), 2-chloroadenosine (pEC(50)=7.3 +/-0.2) and endothelial-depe ndent ADP, but not sodium nitroprusside (SNP). K-ATP channel blockade with 5 muM glibenclamide increased resistance by similar to 80% and inhibited re sponses to CGS21680 in control (pEC(50)=8.3 +/-0.1) and L-NOARG-treated hea rts (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). 6 In summary, mouse coronary vessels are more sensitive to adenosine than r at vessels. A(2A) adenosine receptors mediate dilation in mouse coronary ve ssels vs A(2B) receptors in rat. Responses in the mouse involve a sensitive NO-dependent response and K-ATP-dependent dilation.