Coronary Artery Vasodilation in the Canine

The role of β1- and β2-receptors as modulators of coronary artery vasodilation was studied in the anesthetized dog. The left circumflex coronary artery was cannulated and perfused under constant pressure with blood drawn from the right femoral artery. Coronary blood flow and myocardial contractile force were measured with a cannulating electromagnetic How probe and Walton-Brodie strain gauges, respectively. The left stellate ganglion was isolated distally, and the postganglionic nerves were stimulated with a bipolar electrode. Coronary artery blood How and regional myocardial contractile force increased in response to stellate nerve stimulation and to the intracoronary administration of norepinephrine (NE), isoproterenol (ISO), and zinterol (ZIN) before selective β1-adrenergic receptor blockade with ce-liprolol (0.3 mg/kg intravenously, i.v.). The administration of celiprolol inhibited the positive inotropic response to both stellate stimulation and to the intracoronary administration of the selected β-adrenergic receptor agonists. The increase in coronary artery blood flow observed in response to stellate stimulation or to the intracoronary administration of NE was converted to a decrease in flow in the presence of celiprolol. In contrast, however, the intracoronary administration of ISO or ZIN continued to cause coronary vasodilation despite the presence of β1-selective adrenergic receptor blockade with celiprolol. Addition of propranolol (1.0 mg/kg i.v.) in the presence of celiprolol completely inhibited the increase in coronary blood flow in response to ISO and ZIN. The data demonstrate that physiological changes in coronary blood flow are mediated by β1-adrenergic receptors and that while β1-adrenergic receptors do exist in the canine coronary vascular bed, they are not involved in coronary vasodilation in response to sympathetic nerve stimulation. The results also demonstrate that the intracoronary administration of NE or stellate nerve stimulation in the presence of β1 selective adrenergic receptor blockade can result in an increase in coronary artery resistance.