β-1 adrenoceptors and AT1 receptors may not be involved in catecholamine-induced lethal arrhythmias1

• Published in: Canadian journal of physiology and pharmacology Vol. 97; no. 6; pp. 570 - 576
• Main Authors: Adameova, Adriana, Elimban, Vijayan, Ganguly, Paul K, Dhalla, Naranjan S
• Format: Journal Article
• Language: English
• Published: NRC Research Press 2019
• Subjects: adrenoceptors; adrénergiques; arythmies provoquées par les catécholamines; AT1 receptors; atenolol; blocage des récepteurs; catecholamine-induced arrhythmias; catécholamines plasmatiques; losartan; plasma catecholamines; récepteurs AT1; récepteurs β
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2018-0531

An excessive amount of catecholamines produce arrhythmias, but the exact mechanisms of this action are not fully understood. For this purpose, Sprague–Dawley rats were treated with or without atenolol, a β 1 -adrenoceptor blocker (20 mg/kg per day), for 15 days followed by injections of epinephrine for cumulative doses of 4 to 128 μg/kg. Another group of animals were pretreated with losartan, an angiotensin receptor (AT1) blocker (20 mg/kg per day), for comparison. Control animals received saline. Varying degrees of ventricular arrhythmias were seen upon increasing the dose of epinephrine, but the incidence and duration of the rhythm abnormalities as well as the number of episodes and severity of arrhythmias were not affected by treating the animals with atenolol or losartan. The levels of both epinephrine and norepinephrine were increased in the atenolol-treated rats but were unchanged in the losartan-treated animals after the last injection of epinephrine; the severity of arrhythmias did not correlate with the circulating catecholamine levels. These results indicate that both β 1 -adrenoceptors and AT1 receptors may not be involved in the pathogenesis of catecholamine-induced arrhythmias and support the view that other mechanisms, such as the oxidation products of catecholamines, may play a crucial role in the occurrence of lethal arrhythmias.