Cardiac Augmentation Can Be Maintained by Continuous Exposure of Intrinsic Cardiac Neurons to a β-Adrenergic Agonist or Angiotensin II

Abstract

The purpose of this work was to determine whether constant increases in cardiac rate and force can be induced by continuous exposure (20 min) of intrinsic cardiac neurons to pharmacological agents which activate such neurons. Intrinsic cardiac neurons within the ventral right atrial ganglionated plexus were activated by constant infusions of dobutamine or angiotensin II (100 μM/min for 10 min followed by 200 μM/min for 10 min) via their local arterial blood supply in 12 artificially ventilated, open chest anesthetized dogs while monitoring heart rate and indices of regional cardiac contractility. The results were as follows: (1) Dobutamine (100 μM/min for 10 min) enhanced intrinsic cardiac neuronal activity by 195% at first, neuronal activity declining thereafter to +79% of control values in the continued presence of this agonist. When the dose of dobutamine was doubled (200 μM/min for 10 min) neuronal activity increased +179% above control values and remained elevated, as did heart rate as well as right and left ventricular contractility. (2) Angiotensin II (100 μM/min) increased neuronal activity at first, with neuronal activity decreasing gradually thereafter such that after 5 min of exposure activity reached control values. Neuronal activity did not increase further when neurons were subsequently exposed to a higher dose of angiotensin II (200 μM/min). Heart rate and ventricular contractility were increased initially more by angiotensin II than by dobutamine. However, cardiac indices fell thereafter concomitant with reductions in neuronal activity as the exposure to angiotensin II continued. Thus although cardiac rate and force initially were increased more by angiotensin II than by dobutamine, similar augmentation of cardiac indices was achieved by sustained exposure of a population of intrinsic cardiac neurons to either agent. In conclusion, heart rate and ventricular contractility can be enhanced for relatively prolonged periods of time by continuous exposure of a population of intrinsic cardiac neurons to a β-adrenoceptor agonist or angiotensin II, with the β- adrenoceptor agonist inducing more consistent cardiac augmentation than angiotensin II.