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本实验室曾经报道静脉注射安定对于清醒、麻痹、人工呼吸的家兔具有减低膈神经放电幅度、加快呼吸频率,缩短吸气时程(T_I)和呼气时程(T_E),降低动脉血压等作用。本工作在35只家兔中进一步分析了某些药物对安定的这些作用的影响。GABA 降低膈神经放电幅度和动脉血压,这与安定的作用相同,但 GABA 延长T_I、T_E和减慢呼吸频率,与安定的作用相反。事先用氨基酸脱羧酶抑制剂异烟肼处理,或用 GABA 受体拮抗剂印防己毒素处理,可阻遏安定减低膈神经放电幅度的作用。在事先用印防己毒素处理的家兔中,可见安定缩短 T_IT_E的作用不受影响。异烟肼或印防己毒素还能部分对抗安定的降压效应。阿片受体拮抗剂纳洛酮和5-HT 受体拮抗剂赛庚啶都不能阻遏安定降低膈神经放电幅度和动脉血压的作用。上述结果提示安定降低膈神经放电幅度的作用可能通过 GABA 这一中间环节,而内啡肽和5-HT可能不起重要作用。安定的降压作用需要有内源性 GABA 参与才得以持续较长时间,在减少GABA 或阻断 GABA 受体后,安定只有短暂的降压作用。
It has been reported in our laboratory that intravenous diazepam can reduce the amplitude of phrenic nerve discharge, accelerate the respiratory rate, shorten the inspiratory time (T_I) and expiratory time (T_E), lower the arterial blood pressure, etc. in awake, paralyzed and resuscitated rabbits effect. This work further analyzed the effect of some drugs on these effects of diazepam in 35 rabbits. GABA decreased phrenic nerve discharge amplitude and arterial blood pressure, which is the same with diazepam, but GABA prolong T_I, T_E and slow down the respiratory rate, and the role of diazepam. Pretreatment with isoniazid, an amino acid decarboxylase inhibitor, or picrotoxin, a GABA receptor antagonist, can counteract the effects of diazepam on reducing the magnitude of phrenic nerve discharge. In rabbits previously treated with picrotoxin, the effect of diazepam shortening T_IT_E was unaffected. Isoniazid or picrotoxin can also partially antagonize the hypotensive effect of diazepam. Both naloxone, an opioid receptor antagonist, and cyproheptadine, a 5-HT receptor antagonist, failed to suppress the effects of diazepam on lowering phrenic nerve discharge amplitude and arterial blood pressure. These results suggest that diazepam may reduce the amplitude of phrenic nerve discharge through the middle of GABA, whereas endorphins and 5-HT may not play an important role. Diazepam requires the participation of endogenous GABA to continue for a long time, after reducing GABA or blocking GABA receptor, diazepam only short-term antihypertensive effect.