基础条件和麻醉类型对周围给予γ-氨基丁酸心血管反应的影响差异。

Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia.

作者信息

Giuliani S, Maggi C A, Meli A

出版信息

Br J Pharmacol. 1986 Jul;88(3):659-70. doi: 10.1111/j.1476-5381.1986.tb10248.x.

DOI:10.1111/j.1476-5381.1986.tb10248.x

PMID:3742154

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1916971/

Abstract

The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. gamma-aminobutyric acid (GABA) were investigated in guinea-pigs anaesthetized with barbitone or urethane. GABA (0.1-10 mg kg-1) produced a transient 'depressive' effect on cardiovascular parameters which in barbitone-anaesthetized animals was followed by a transient 'excitatory' effect. Resting cardiovascular parameters were higher in urethane-as compared to barbitone-anaesthetized animals. Picrotoxin pretreatment (2 mg kg-1, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone-anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase. Hexamethonium (20 mg kg-1, i.v.) suppressed or reduced markedly the GABA-induced cardiovascular changes both in barbitone- or urethane- anaesthetized animals. Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the 'excitatory' type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments. Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5-aminovaleric acid) mimicked the 'excitatory' effect of GABA in reserpine pretreated animals anesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (+/-)-baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the 'excitatory' cardiovascular effects of GABA. Neither bicuculline nor picrotoxin pretreatment prevented the 'excitatory' cardiovascular effect of i.v. GABA in reserpine pretreated, guinea-pigs anaesthetized with barbitone. In adrenalectomized guinea-pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small 'depressant' effect on cardiovascular parameters. These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: type of anaesthesia resting values of cardiovascular parameters degree of activity of the sympathetic nervous system and catecholamine release from the adrenal medulla.

摘要

在巴比妥或乌拉坦麻醉的豚鼠中研究了静脉注射γ-氨基丁酸（GABA）对心血管系统（血压、心率、心肌收缩力）的影响。GABA（0.1 - 10mg/kg）对心血管参数产生短暂的“抑制”作用，在巴比妥麻醉的动物中随后会出现短暂的“兴奋”作用。与巴比妥麻醉的动物相比，乌拉坦麻醉动物的静息心血管参数更高。预先静脉注射印防己毒素（2mg/kg）对巴比妥麻醉动物中GABA引起的心血管变化几乎没有影响。在预先用印防己毒素处理并用乌拉坦麻醉的动物中，GABA最初使心血管参数降低，随后进入兴奋期。六甲铵（20mg/kg，静脉注射）在巴比妥或乌拉坦麻醉的动物中均显著抑制或减弱了GABA诱导的心血管变化。利血平预处理降低了静息心血管参数。在这些动物中，无论麻醉类型如何，静脉注射GABA的作用仅为“兴奋”型。选择用巴比妥麻醉的利血平预处理动物进行进一步实验。各种GABAA受体激动剂（高牛磺酸、蝇蕈醇、THIP、5-氨基戊酸）模拟了GABA对用巴比妥麻醉的利血平预处理动物的“兴奋”作用，并阻止了随后给予GABA的作用。另一方面，选择性GABAB受体激动剂（±）-巴氯芬有轻微的抑制作用，并未阻止GABA的“兴奋”性心血管作用。在利血平预处理并用巴比妥麻醉的豚鼠中，预先使用荷包牡丹碱或印防己毒素均不能阻止静脉注射GABA的“兴奋”性心血管作用。在肾上腺切除的豚鼠或接受静脉注射酚妥拉明加普萘洛尔的制剂中，GABA对心血管参数仅产生轻微的“抑制”作用。这些发现表明，GABA通过外周作用对心血管功能发挥神经调节作用，该作用受以下因素影响：麻醉类型、心血管参数的静息值、交感神经系统的活动程度以及肾上腺髓质中儿茶酚胺的释放。