Abrahams T P, Taveira DaSilva A M, Hamosh P, McManigle J E, Gillis R A
Department of Pharmacology, Georgetown University, School of Medicine, Washington, DC 20007.
Eur J Pharmacol. 1993 Jul 20;238(2-3):223-33. doi: 10.1016/0014-2999(93)90851-8.
The aim of our study was to determine the role of excitatory amino acids in controlling cardiorespiratory activity. For this purpose we administered an antagonist of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors (kynurenic acid), and an antagonist of the NMDA receptor complex (dizocilpine, more commonly known as MK-801) i.v. to chloralose-anesthetized cats while monitoring tracheal air flow, tidal volume, respiratory rate, inspiratory and expiratory durations, end tidal CO2, arterial blood pressure and heart rate. Administration of kynurenic acid in doses of 350 and 500 mg/kg produced respiratory depression as reflected by decreases in respiratory minute volume and increases in end tidal CO2. Inspiratory duration was increased with both doses and apnea (occurring during expiration) was observed with the high dose. Apnea was preceded by an apneustic pattern of breathing. Both doses resulted in an increase in blood pressure and, with the high dose, a later decrease in blood pressure was noted. Dizocilpine in doses ranging from 0.03 to 1 mg/kg produced dose-related decreases in respiratory minute volume, and increases in end tidal CO2. In addition, dizocilpine produced increases in inspiratory duration, an apneustic pattern of breathing and apnea (occurring during inspiration). Effects on blood pressure were similar to those observed with kynurenic acid. It is concluded that blockade of excitatory amino acid receptors results in pronounced effects on cardiorespiratory activity.
我们研究的目的是确定兴奋性氨基酸在控制心肺活动中的作用。为此，我们静脉注射N-甲基-D-天冬氨酸（NMDA）和非NMDA受体的拮抗剂（犬尿喹啉酸）以及NMDA受体复合物的拮抗剂（地佐环平，更常用的名称是MK-801），同时监测氯醛糖麻醉猫的气管气流、潮气量、呼吸频率、吸气和呼气持续时间、呼气末二氧化碳、动脉血压和心率。静脉注射350和500mg/kg剂量的犬尿喹啉酸会导致呼吸抑制，表现为每分通气量降低和呼气末二氧化碳升高。两种剂量均使吸气持续时间延长，高剂量时观察到呼吸暂停（发生在呼气期）。呼吸暂停之前有长吸式呼吸模式。两种剂量均导致血压升高，高剂量时随后血压下降。剂量范围为0.03至1mg/kg的地佐环平导致每分通气量呈剂量相关降低，呼气末二氧化碳升高。此外，地佐环平使吸气持续时间延长、出现长吸式呼吸模式和呼吸暂停（发生在吸气期）。对血压的影响与犬尿喹啉酸观察到的相似。结论是，兴奋性氨基酸受体的阻断对心肺活动有显著影响。
