Influence of β‐adrenoceptor tone on the cardioprotective efficacy of adenosine A1 receptor activation in isolated working rat hearts

This study investigated the role of β‐adrenoceptors in the cardioprotective and metabolic actions of adenosine A1 receptor stimulation. Isolated paced (300 beats min−1) working rat hearts were perfused with Krebs‐Henseleit solution containing 1.2 mM palmitate. Left ventricular minute work (LV work), O2 consumption and rates of glycolysis and glucose oxidation were measured during reperfusion (30 min) following global ischaemia (30 min) as well as during aerobic conditions. Relative to untreated hearts, N6‐cyclohexyladenosine (CHA, 0.5 μM) improved post‐ischaemic LV work (158%) and reduced glycolysis and proton production (53 and 42%, respectively). CHA+propranolol (1 μM) had similar beneficial effects, while propranolol alone did not affect post‐ischaemic LV work or glucose metabolism. Isoprenaline (10 nM) impaired post‐ischaemic function and after 25 min ischaemia recovery was comparable with 30 min ischaemia in untreated hearts (41 and 53%, respectively). Relative to isoprenaline alone, CHA+isoprenaline improved recovery of LV work (181%) and reduced glycolysis and proton production (64 and 60%, respectively). In aerobic hearts, CHA, propranolol or CHA+propranolol had no effect on LV work or glucose oxidation. Glycolysis was inhibited by CHA, propranolol and CHA+propranolol (50, 53 and 52%, respectively). Isoprenaline‐induced increases in heart rate, glycolysis and proton production were attenuated by CHA (85, 57 and 53%, respectively). The cardioprotective efficacy of CHA was unaffected by antagonism or activation of β‐adrenoceptors. Thus, the mechanism of protection by adenosine A1 receptor activation does not involve functional antagonism of β‐adrenoceptors. British Journal of Pharmacology (2000) 131, 537–545; doi:10.1038/sj.bjp.0703597