安定减低家兔膈神经放电幅度的机制分析

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。

ANALYSIS OF DEPRESSANT EFFECT OF DIAZEPAM ON THE AMPLITUDE OF PHRENIC NERVE DISCHARGE IN RABBITS

Our previous study indicated that in awake rabbits diazepam depressed the am-plitude of phrenic nerve discharge,increased respiratory rate,shortened both the in-spiratory and expiratory durations(T_I and T_E)and lowered arterial blood pres-sure.In the present experiments,the effects of some drugs on the above-mentioneddiazepam actions were further examined in 35 rabbits.GABA caused depressionof the amplitude of phrenic discharge and blood pressure,an effect similar to that ofdiazepam.But,different from diazepam,GABA prolonged both T_I and T_E,andthus decreased the respiratory rate.Pretreatment of either isoniazid,an aminoacid decarboxylase inhibitor,or GABA receptor antagonist picrotoxin prevented thedepressant effect of diazepam on the amplitude of phrenic discharge.However,theshortening of T_I and T_E by diazepam was not affected in pretreatment of picroto-xin.When given alone,diazepam produced a fall on blood pressure lasting for morethan one hour.In isoniazid or picrotoxin pretreated rabbits,however,diazepamexhibited a transient depressor effect lasting only 2 to 10 minutes.Neither naloxone(an opiate receptor antagonist)or cyproheptadine(a serotonin receptor antagonist)pretreatment affected the depressant effects of diazepam upon the amplitude ofphrenic discharge and blood pressure.The results obtained suggest that the de-pressant effect of diazepam on the amplitude of phrenic discharge is mediated byGABA,while endorphins and serotonin seem not to be involved.Prolongationof the depressor effect of diazepam is possibly attributable to the participation ofGABA,since following block of GABA synthesis or GABA receptors diazepam lower-ed blood pressure only transiently.