Pharmacological evidence for differences in the beta-adrenoreceptor populations mediating atrial and ventricular chronotropic responses in the unanaesthetized dog

The beta-adrenoreceptor populations mediating atrial and ventricular chronotropic responses were studied comparatively in the unanaesthetized dog with chronic atrio-ventricular block. With this aim, we first compared the increases in atrial and ventricular rate induced by isoprenaline. We then compared the reductions of this isoprenaline-induced atrial and ventricular cardio-acceleration, observed after administration of cumulative doses of propranolol and alprenolol, both non-selective beta-adrenoreceptor blocking agents, and metoprolol, a blocking agent selective for beta 1-adrenoreceptors. Isoprenaline induced a much more intense stimulation of atrial chronotropic beta-adrenoreceptors than of ventricular chronotropic beta-adrenoreceptors, whether or not the cholinoreceptors were blocked. Similarly, all three beta-blocking agents induced a more intense blockade of atrial chronotropic beta-adrenoreceptors than of ventricular chronotropic beta-adrenoreceptors, whatever the dose of isoprenaline considered and whether or not the cholinoreceptors were blocked. These results cannot be readily explained by quantitative differences in the distribution of beta 1- and beta 2-adrenoreceptors in the heart, given the identical effects obtained with metoprolol, propranolol and alprenolol. Therefore, beta-adrenoreceptor populations are not identical throughout the nodal tissue, and in particular, differences occur between beta-adrenoreceptors in the sinus node mediating atrial chronotropic responses and those in the His bundle mediating ventricular chronotropic responses, which might be linked to differing sensitivities of these beta-adrenoreceptor populations.