Hof R P, Hof A, Scholtysik G, Menninger K
J Cardiovasc Pharmacol. 1984 May-Jun;6(3):407-16. doi: 10.1097/00005344-198405000-00006.
The effects of PN 200-110 (PN), isopropyl 4-(2,1,3- benzoxadiazol -4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate , on the cardiovascular system were investigated. In chloralose-urethane-anesthetized cats PN decreased blood pressure (BP) and heart rate (HR) and increased cardiac output (CO) and total peripheral resistance dose dependently after intravenous doses of 1-10 micrograms/kg. Regional blood flow changes effected by an intravenous dose of 10 micrograms/kg were measured with microspheres. Flow to the heart, brain, and skeletal muscle increased selectively, and intramyocardial flow was redistributed in favor of the left ventricular subepicardial layer. The duration of action differed for various effects. The bradycardia was short lasting, and the cerebral vasodilatation persisted longest. It was not possible to predict the duration of action of PN on different target tissues by observing only one variable such as BP. Chloralose-urethane-anesthetized open-chest dogs appeared to be more sensitive to PN than cats. A dose of 3 micrograms/kg i.v. markedly increased coronary flow, lowered BP, increased CO, and tended to lower HR and to increase myocardial contractility. Myocardial oxygen consumption was lowered. PN did not alter diastolic excitation threshold or any electrocardiographic intervals in closed-chest anesthetized dogs. Absence of myocardial depression, potent vasodilator activity, and long duration of action might render PN useful for the treatment of hypertension and angina pectoris.
研究了PN 200 - 110（PN），即4 -（2,1,3 - 苯并恶二唑 - 4 - 基）- 1,4 - 二氢 - 5 - 甲氧基羰基 - 2,6 - 二甲基 - 3 - 吡啶羧酸异丙酯对心血管系统的影响。在氯醛糖 - 乌拉坦麻醉的猫中，静脉注射剂量为1 - 10微克/千克后，PN剂量依赖性地降低血压（BP）和心率（HR），并增加心输出量（CO）和总外周阻力。用微球测量静脉注射10微克/千克剂量后引起的局部血流变化。流向心脏、大脑和骨骼肌的血流量选择性增加，心肌内血流重新分布，有利于左心室心外膜下层。不同效应的作用持续时间不同。心动过缓持续时间短，脑血管扩张持续时间最长。仅通过观察一个变量（如BP）无法预测PN对不同靶组织的作用持续时间。氯醛糖 - 乌拉坦麻醉的开胸犬似乎比猫对PN更敏感。静脉注射3微克/千克的剂量显著增加冠状动脉血流量，降低血压，增加心输出量，并倾向于降低心率和增加心肌收缩力。心肌耗氧量降低。PN在闭胸麻醉犬中不改变舒张期兴奋阈值或任何心电图间期。缺乏心肌抑制作用、强大的血管舒张活性和较长的作用持续时间可能使PN对治疗高血压和心绞痛有用。
