Merrick A, Hadley W M, Holcslaw T L
Res Commun Chem Pathol Pharmacol. 1979 Jul;25(1):13-22.
Atropine sulfate causes bradycardia in doses which are greater than the usual anticholinergic doses producing tachycardia (Shucard and Andrew, 1977, Res. Comm. Chem. Path. Pharmacol. 16, 401-410). The present study was designed to evaluate the effects of large doses of atropine sulfate on heart rate and systemic blood pressure in rats. Six groups of urethane anesthetized, male, Sprague Dawley rats (200-450 g) were injected with varying doses of atropine via the jugular vein. Groups I through IV received 5 mg/kg, 20 mg/kg, 40mg/kg and 80 mg/kg, respectively. Group V was bilaterally vagotomized before the injection of 80 mg/kg of atropine. Animals in Group VI were bilaterally vagotomized and pretreated with propranolol-HCl before injection of 40 mg/kg of atropine. Atropine caused a significant (p less than 0.005) dose-dependent reduction in both heart rate and blood pressure. The negative chronotropic property of atropine shown in these experiments is in agreement with recent in vitro and in vitro studies. The cause of bradycardia in these doses appears to be an intrinsic property of atropine rather than being centrally mediated. Possible direct action by atropine on peripheral vascular resistance is discussed.
硫酸阿托品在剂量大于通常产生心动过速的抗胆碱能剂量时会引起心动过缓（舒卡德和安德鲁，1977年，《研究通讯：化学病理与药理学》16卷，401 - 410页）。本研究旨在评估大剂量硫酸阿托品对大鼠心率和全身血压的影响。将六组经乌拉坦麻醉的雄性斯普拉格 - 道利大鼠（200 - 450克）通过颈静脉注射不同剂量的阿托品。第一组至第四组分别接受5毫克/千克、20毫克/千克、40毫克/千克和80毫克/千克的剂量。第五组在注射80毫克/千克阿托品前进行双侧迷走神经切断术。第六组在注射40毫克/千克阿托品前进行双侧迷走神经切断术并预先用盐酸普萘洛尔处理。阿托品导致心率和血压均出现显著的（p小于0.005）剂量依赖性降低。这些实验中显示的阿托品的负性变时特性与最近的体外和体内研究一致。这些剂量下心动过缓的原因似乎是阿托品的固有特性，而非中枢介导。文中讨论了阿托品对外周血管阻力可能的直接作用。
