Evidence for the role of A2B adenosine receptor in the regulation of vascular tone using A2B KO mice

Abstract

Adenosine, an endogenous nucleoside, exerts its effects through its four receptor subtypes (AR): A1, A2A, A2B, and A3. Adenosine is involved in the regulation of vascular tone where its effects are subtype‐dependent. The contribution of ARs needs to be further investigated in order to better understand the heterogeneity of vasculature responses. In mice aorta, A2A AR is known to be involved in vascular relaxation, however, the role of A2B AR has not been studied in this tissue. To investigate this, we performed organ bath experiments. Tissues with <40% ACh relaxation to PE (10−6M) contraction were excluded (endothelial integrity). NECA, a non‐selective AR agonist, induced a significantly higher contraction in A2B KO compared to WT (21.8±3.2% contraction vs 21.9±8.5% relaxation at 10−5M, p<0.01) showing that activation of A2B AR may induce relaxation. CCPA, a selective A1 agonist, induced contraction (38.9±6.3% at 10−6M) was significantly reduced in A2B KO (5.9±7.8% at 10−6M, p<0.01) suggesting the down‐regulation of A1 AR. Cl‐IBMECA, a selective A3 agonist, showed significantly lower contraction in A2B KO compared to WT (14.6±3.3% vs 42.9±5.3% at 10−6M, respectively) further suggesting the down‐regulation of A3 AR in A2B KO. These data show a relationship between A2B and A1 and A3 ARs which must be taken into account in the control of vascular tone. Supported by HL027339, HL094447, HL071802, and T‐32 HL090610.