Effects of β-Adrenergic Blocking Agents on Positive Chronotropic Responses to Exercise in Conscious Dogs

Abstract

The effects CS-359 (5-methyl-8-(2-hydroxy-3-t-butylaminopropoxy) coumarin hydrochloride), a new β-adrenergic blocking agent, on positive chronotropic responses to Isoproterenol and exercise were compared with those of Propranolol in conscious beagle dogs. The heart rate was measured from the electrocardiogram ABL-I recorded with biopotential skin electrodes. Exercise was performed for 3 min on a motor-driven treadmill. Heart rate rose rapidly at first and then stabilized at a certain level making a plateau. The level of heart rate in the plateau was in parallel with amount of the exercise within a range from 90 to 200 m/min. l-Isoproterenol (0.2μg/kg) was administered through an indwelling cannula in the ear vein. Following oral administration of a β-adrenergic blocking agent, each animal received Isoproterenol or treadmill exercise at 30 or 60 min intervals for 6 hr. Dose-response curves for β-adrenergic blocking activity against Isoproterenol tachycardia revealed that CS-359 was 2 to 3 times more potent than Propranolol. Similar results were obtained in preventing Exercise tachycardia; e. g., 0.3 mg/kg of CS-359 and 1.0 mg/kg of Propranolol equally inhibited the tachycardia. The tachycardia induced by exercise, however, could not be completely prevented even by the treatment with an extremely high dose of β-adrenergic blocking agents, while Isoproterenol tachycardia was abolished by a sufficient high dose of the blockers. Therefore, Exercise tachycardia may partly be attributed to the inhibition of vagal tone. Experiments with β-adrenergic, parasympathetic and combined blockades also supported the contribution of the vagal inhibition.