Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta 2 adrenoceptors in the sinoatrial node.
To test the hypothesis that beta 2 adrenergic receptors mediate the chronotropic more than the inotropic response to endogenous catecholamines the effects on the haemodynamic responses to exercise in dogs of the beta 1 specific antagonist atenolol were compared with those of the non-selective beta antagonist propranolol. Heart rate, left ventricular dP/dt at 40 mmHg developed pressure (dP/dt40), and oxygen consumption (VO2) were determined at seven to eight exercise levels in 16 chronically instrumented adult mongrel dogs with and without beta blockade. In doses that produced equivalent suppression of resting heart rate, propranolol and atenolol affected dP/dt40 similarly at all exercise levels. In contrast to atenolol, which affected heart rate equally at all workloads, propranolol inhibited heart rate more as the workload increased, resulting in a 1.55-fold greater percentage inhibition of chronotropy at a VO2 of 60 ml.Kg-1.min-1 a than at a VO2 of 30 ml.kg-1.min-1. These results are compatible with the hypothesis that, although beta 2 receptors appear to have little influence over cardiac inotropy during exercise, sinoatrial beta 2 receptors may be stimulated by circulating catecholamines and contribute greatly to sympathetic modulation of heart rate during heavy exercise in dogs.
Friedman
D B
DB
Department of Internal Medicine, University Texas Health Science Center, Dallas.
Musch
T I
TI
Williams
R S
RS
Ordway
G A
GA
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012849:Sinoatrial Node / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011433:Propranolol