a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University 832 32 Bratislava, Odbojarov 10, Slovakia.
b Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre and Department of Physiology & Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
Can J Physiol Pharmacol. 2019 Jun;97(6):570-576. doi: 10.1139/cjpp-2018-0531. Epub 2018 Dec 17.
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-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-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.
过量的儿茶酚胺会导致心律失常，但这种作用的确切机制尚未完全了解。为此，将 Sprague-Dawley 大鼠用或不用阿替洛尔（每天 20mg/kg）处理 15 天，然后注射肾上腺素，累积剂量为 4 至 128μg/kg。另一组动物用氯沙坦（一种血管紧张素受体（AT1）阻滞剂，每天 20mg/kg）预处理，作为比较。对照组动物给予生理盐水。随着肾上腺素剂量的增加，观察到不同程度的室性心律失常，但用阿替洛尔或氯沙坦治疗动物并不影响节律异常的发生率和持续时间，以及发作次数和心律失常的严重程度。阿替洛尔处理的大鼠中肾上腺素和去甲肾上腺素的水平均升高，但最后一次注射肾上腺素后，氯沙坦处理的动物中肾上腺素和去甲肾上腺素的水平不变；心律失常的严重程度与循环儿茶酚胺水平无关。这些结果表明，β-肾上腺素受体和 AT1 受体可能都不参与儿茶酚胺引起的心律失常的发病机制，并支持这样一种观点，即其他机制，如儿茶酚胺的氧化产物，可能在致命性心律失常的发生中起关键作用。
