Interaction between Adenosine and beta-adrenergic receptors in regulating vascular tone in mouse mesenteric arteries.

Adenosine (AR) and β‐adrenergic receptors (βR) are GPCRs involved in the regulation of cardiovascular function. Adenosine is an endogenous nucleoside which controls local blood flow through activation of four subtypes of ARs. Stimulation of A 1 and A 3 ARs produce contraction while A 2A and A 2B ARs cause relaxation in mouse aorta and mesenteric arteries (MAs). Stimulation of β 1 R causes increase in heart rate and contractile force whereas β 2 R produces relaxation of blood vessels. Reportedly, A 1 AR, β1R, and β2R form heterodimers in human heart. Hetero‐dimerization between A 1 AR and βR leads to altered receptor pharmacology, functional coupling, and intracellular signaling pathways. Importantly, stimulation of the myocytes with isoproterenol (βR agonist) inhibits the effect of A 1 AR activation on the co‐localization of protein kinase C‐ɛ involving protein kinase A. Thus, a complex interaction between signaling cascades of A 1 AR and β1R exists, which may regulate cardiovascular function. In the present study, we aimed to determine whether interaction between β 1 R and ARs exists in regulating vascular tone in mouse aorta and MAs. We measured mean arterial blood pressure (MABP), protein expression, organ bath (aorta) and DMT (MA) muscle tension in β 1 R KO and WT mice. Our non‐invasive CODA tail cuff BP (mmHg) data showed significant reduction in MABP in β 1 R KO mice. The MABP in β 1 R WT mice was 83.4 ± 3; whereas 68.9 ± 3 (p<0.05) in β 1 R KO mice. Our DMT experiments revealed that β 1 R was partly involved in the vascular relaxation response to isoproterenol. Significantly reduced relaxation response to isoproterenol was observed in A 1 AR KO mice MAs. Importantly, significantly enhanced contraction to CCPA (A 1 AR agonist) was observed in β 1 R KO mice MAs. These contractile responses were blocked by HET0016 (Cyp4A inhibitor). NECA (non selective ARs agonist) induced responses were comparable in MAs. Furthermore, our vascular studies revealed significantly reduced PE and ACh induced contraction in MAs of β 1 R KO mice whereas KCl induced responses were comparable. Our western blot analysis revealed higher A 1 AR and comparable Cyp4A expression levels in MAs. Our studies in aorta revealed comparable CCPA induced contraction in β1R WT and KO mice. In addition, comparable A 1 AR and Cyp4A expression levels and vascular responses to KCl, ACh and PE were observed in aorta. In conclusion, our data revealed a possible interaction between β 1 R and A 1 AR at a vascular level in MAs. This unique receptor cross‐talk may enlighten the important signaling responses controlling vascular function. Support or Funding Information Supported by HL 027339 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .