Functional profile of adenosine receptor subtypes in mouse mesenteric artery

Adenosine, an autacoid, plays an important role in regional blood flow regulation. Four adenosine receptor subtypes (A 1 , A 2A , A 2B , and A 3 AR) are known to mediate adenosine‐induced vasodilation or vasoconstriction. Its function in certain vascular beds depends upon the distribution of its receptor subtypes. We studied the vascular effects of various adenosine receptor agonists in isolated mesenteric arteries from 4 AR knockout (KO) mice (A 1 , A 2A , A 2B , and A 3 ) and their wild type (WT). Eight first branches of the superior mesenteric arteries were isolated from each mouse and mounted on an organ bath linked to isometric myograph (DMT). Concentration‐response curves (CRC) to adenosine, NECA (non specific agonist), CCPA (A 1 specific agonist), CGS‐21680 (A 2A specific agonist), BAY 60–6583 (A 2B specific agonist), and Cl‐IB‐MECA (A 3 specific agonist) were constructed (10 −11 –10 −4 M). Adenosine and NECA induced only dilation (10 −5 and 10 −4 M of adenosine and 10 −6 and 10 −5 M of NECA). Constriction was observed only in A 2B KO induced by adenosine and NECA, which showed up to 40% increase in tension by both agonists (from 10 −6 to 10 −4 by adenosine and from10 −8 to 10 −5 by NECA). CCPA induced a significant constriction (only at 10 −8 –10 −7 M) except A 1 KO. BAY 60–6583 induced concentration dependent dilation (10 −7 –10 −5 M) in WT and no response in A 2B KO except at 10 −5 M. Interestingly, in other AR KOs (A 1 , A 2A , and A 3 ), the CRC for BAY 60–6583 shifted to the left when compared to WT suggesting an up‐regulation of A 2B AR. No responses were noted to CGS‐21680 in all four KOs. Cl‐IB‐MECA induced dilation at concentration greater than 10 −7 M and no differences were found in all the KOs and WT. Our data suggest that A 2B AR is the predominant AR subtype, while A 1 AR plays a modulating role in the control of resistance vessel tone in this tissue. Support: NIH grants HL027339, HL094447, HL071802