Heavner J E, Shi B, Pitkänen M
Department of Anesthesiology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Life Sci. 1995;57(7):715-28. doi: 10.1016/0024-3205(95)00323-x.
The effects of N omega-nitro-L-arginine methyl ester (L-NAME) i.v. and nitric oxide (NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats. Cocaine (4 mg/kg/min i.v.) produced seizures then isoelectric electrocephalographic (isoEEG) activity as well as an initial increase in systolic blood pressure and heart rate, then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME (2 mg/kg/min i.v.) for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8). Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. No inhalation (80 ppm) did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular system (lower dose for arrhythmias and asystole), but does not affect the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.
在轻度麻醉、麻痹并机械通气的大鼠中，研究了静脉注射Nω-硝基-L-精氨酸甲酯（L-NAME）和吸入一氧化氮（NO）对可卡因全身综合反应的影响。可卡因（4mg/kg/min静脉注射）会引发癫痫，随后出现脑电图等电位（isoEEG）活动，同时收缩压和心率最初会升高，随后心血管系统逐渐抑制，最终导致心搏停止。与生理盐水处理的动物相比，用L-NAME（2mg/kg/min静脉注射）预处理30分钟可显著降低癫痫发作的发生率（生理盐水组7/8；L-NAME组3/8）。与生理盐水组相比，L-NAME处理的动物中，引发心律失常、isoEEG和心搏停止的可卡因剂量显著更低。L-NAME不影响对可卡因的收缩压峰值和心率反应。在对照动物中，吸入NO（80ppm）不影响对可卡因的中枢神经系统和心血管反应，但增强了L-NAME对可卡因毒性的影响。结果表明，L-NAME预处理可降低可卡因对中枢神经系统的刺激作用（降低癫痫发作发生率），增强其对中枢神经系统（产生isoEEG的剂量更低）和心血管系统（引发心律失常和心搏停止的剂量更低）的抑制作用，但不影响可卡因的心血管刺激作用。在正常或一氧化氮产生受抑制的动物中，吸入NO不能预防可卡因的任何全身效应。
