Coronary flow and cardiac responses to adenosine in beta‐1 adrenergic knockout mice

Both adenosine and beta adrenergic receptors play prominent roles in cardiovascular function. There are reports in the literature that cross‐talk exists between adenosine receptors and beta adrenergic receptors. Of the 3 major beta adrenergic receptors, beta‐1 (B‐1) is the predominant subtype in the heart. Using in vivo ultrasound techniques and ex vivo isolated heart experiments, we measured coronary flow (CF) and cardiac responses to isoproterenol (non‐specific beta‐1 and beta‐2 agonist) and adenosine in beta‐1 adrenergic knockout (KO) mice and their wild type (WT). Based upon ultrasound experiments, baseline CF (by measuring left coronary artery, 0.36± 0.13 in WT vs 0.31±0.11 in KO, mL/min), stroke volume (SV, 30.25±6.57 in WT vs 28.86±7.63, μL), and ejection fraction (EF, 54.68±5.18 in WT vs 55.86±7.07 in KO, %) were not different between WT (n=10) and KO (n=8). But heart rate (HR, 501±54 in WT vs 432±38 in KO, BPM) and cardiac output (CO, 15.23±4.03 in WT vs 12.31±2.83 in KO, mL/min) were lower in KO. Bolus isoproterenol (i.v. injection; 0.1 mg/kg) increased CF (1.61±0.67 mL/min/kg), HR (643±46 BPM), and EF (82.63±8.81 %) in WT, but not in KO. In isolated heart experiments, there were no significant differences between baseline CF (14.37±3.45 in WT vs 17.43±2.34 mL/min/kg of heart weight) and left ventricular developed pressure (LVDP, 79.61±19.81 in WT vs 74.66±26.39 in KO, mmHg), but baseline HR was higher in KO mice (365±16 in WT vs 416±31 in KO, BPM). KO mice were less responsive to adenosine (10 −8 to 10 −5 M) to CF, HR, and LVDP ( Figs.). In conclusion, the deletion of B‐1 adrenergic receptor not only removes cardiovascular responses to isoproterenol, but also reduces their responsiveness to adenosine, supporting a functional cross‐talk between adenosine receptors and beta‐1 receptor. Support or Funding Information NIH HL 027339 and 094447