Hedner J
Acta Physiol Scand Suppl. 1983;524:1-109.
Neuropharmacological mechanisms in central regulation of respiration in anesthetized rats were studied in a whole body plethysmographic model. Neurotransmitter agonists and antagonists were administered intracerebroventricularly or locally into the brain and the respiratory pattern was analysed. The four anesthetics: enflurance (E), halothane (H), pentobarbital sodium (P) and urethane (U) were found to have different effects on central respiratory regulation. Respiratory frequency was higher after H and U compared to after E and P. Animals anesthetized with H exhibited a lower inspiratory drive and a slightly depressed sensitivity to CO2. The responses to the neuropeptides substance P and TRH as well as the amino acid neurotransmitter GABA were partly modified after the different forms of anesthesia. Apomorphine (i.c.v) induced a biphasic, haloperidol reversible, respiratory response in H- and U- (but not in E- and P-) anesthetized rats. The initial bradypnoic response might be due to a decreased sensitivity to afferent vagal signals, while the following tachypnoic phase might be elicited by dopaminergic mechanisms at posterior diencephalic and upper midbrain levels (hypoxic, hypercapnic tachypnea). The tachypnoic response was inhibited by a graded exposure to CO2. The effects of different neurotransmitters were further analysed in H-anesthetized animals. GABA and the GABA agonist muscimol exerted a depressant effect on ventilation in contrast to the GABA-like drugs GHBA an baclofen. Exogenous GABA depressed all respiratory parameters studied exept for inspiratory time and was found to affect mainly respiratory timing mechanisms. An increase in endogenous GABA levels induced by the GABA transaminase inhibitor AOAA blunted the respiratory response to CO2 and induced a ventilatory depression similar to that seen after exogenous GABA. A significance correlation between brain stem GABA levels and respiratory duty cycle was found. The tripeptide TRH induced a marked tachypnea due to the extrahypothalamic actions of the peptide. A delay in the response was seen after local injection into the nucleus tractus solitarius and the tachypnea was abolished by CO2 exposure. The ventilatory effects might be elicited by mechanisms similar to those involved in the tachypnoic response to apomorphine. The tachypnea was potentiated by GABA (possibly due to that both agents act on inspiratory off-switch lowering mechanism) and by methylatropine or naloxone (possibly due to secondary pertubation by cholinergic or enkephalinergic mechanisms). A stimulation of ventilation (increase in tidal volume) was seen after substance P (SP) due to an increase in inspiratory drive and o
在全身体积描记模型中研究了麻醉大鼠呼吸中枢调节的神经药理学机制。将神经递质激动剂和拮抗剂经脑室或局部注入脑内，并分析呼吸模式。发现四种麻醉剂：恩氟烷（E）、氟烷（H）、戊巴比妥钠（P）和氨基甲酸乙酯（U）对中枢呼吸调节有不同影响。与E和P麻醉后相比，H和U麻醉后呼吸频率更高。用H麻醉的动物吸气驱动力较低，对二氧化碳的敏感性略有降低。在不同形式的麻醉后，对神经肽P物质和TRH以及氨基酸神经递质GABA的反应部分发生了改变。阿扑吗啡（脑室内注射）在H和U麻醉（但不是E和P麻醉）的大鼠中诱导了双相、氟哌啶醇可逆的呼吸反应。最初的呼吸减慢反应可能是由于对迷走神经传入信号的敏感性降低，而随后的呼吸急促期可能是由间脑后部和中脑上部水平的多巴胺能机制引起的（低氧、高碳酸血症性呼吸急促）。呼吸急促反应被分级暴露于二氧化碳所抑制。在H麻醉的动物中进一步分析了不同神经递质的作用。与GABA样药物γ-羟基丁酸钠和巴氯芬相反，GABA和GABA激动剂蝇蕈醇对通气有抑制作用。外源性GABA除了吸气时间外，降低了所有研究的呼吸参数，并且发现主要影响呼吸定时机制。GABA转氨酶抑制剂氨基氧乙酸诱导的内源性GABA水平升高减弱了对二氧化碳的呼吸反应，并诱导了与外源性GABA后相似的通气抑制。发现脑干GABA水平与呼吸占空比之间存在显著相关性。三肽TRH由于该肽下丘脑外的作用而诱导明显的呼吸急促。局部注射到孤束核后反应延迟，暴露于二氧化碳后呼吸急促消失。通气作用可能由与对阿扑吗啡呼吸急促反应所涉及的机制相似的机制引起。GABA（可能是由于两种药物都作用于吸气切断机制）、甲基阿托品或纳洛酮（可能是由于胆碱能或脑啡肽能机制的继发性扰动）使呼吸急促增强。P物质（SP）后由于吸气驱动力增加而出现通气刺激（潮气量增加）
