Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading.
Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading.
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二氯乙酸酯可阻断吸气流阻负荷期间的内源性阿片类药物作用。
DOI：
10.1152/jappl.1992.72.2.590
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Edelman,NH
中科院分区：
文献类型：
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作者：
Petrozzino,JJ;Scardella,AT;Santiago,TV;Edelman,NH
未麻醉山羊的吸气流阻负荷（IRL）引起内源性阿片类物质的中枢加工，这伴随着几个呼吸肌的抑制。负责介导这种现象的外周刺激是未知的。我们假设乳酸介导IRL期间内源性阿片样物质的释放。用生理盐水或乳酸形成阻断剂二氯乙酸盐（DCA; 50 mg/kg iv）预处理未麻醉山羊，并使其经受IRL（50 cm H2O.l-1.s）120 min，随后纳洛酮（NLX; 0.3 mg/kg iv）。测量膈肌（EMGdi）、外斜肌（EMGeo）和外肋间肌（EMGei）的肌电活动，并表示为潮气末CO2为8%时的活动百分比。DCA阻断了IRL 120分钟后观察到的NLX诱导的所有EMG增强，如下所示（平均值+/- SE）：Δ EMGdi从20.8 +/- 5.6%（生理盐水）至1.2 +/- 2.7%（DCA），Δ EMGeo从116.6 +/- 30.9%（生理盐水）至5.3 +/- 11.4%（DCA），Δ EMGei从43.8 +/- 11.3%（生理盐水）至-4.5 +/- 5.6%（DCA）（所有P均小于0.05，DCA vs.生理盐水）。我们的结论是乳酸产生的收缩呼吸肌是刺激负责内源性阿片途径激活在IRL。
Inspiratory flow-resistive loading (IRL) in unanesthetized goats causes central elaboration of endogenous opioids, which is accompanied by inhibition of several respiratory muscles. The peripheral stimulus responsible for mediating this phenomenon is unknown. We hypothesized that lactic acid mediates release of endogenous opioids during IRL. Unanesthetized goats were pretreated with either saline or dichloroacetate (DCA; 50 mg/kg iv), a blocker of lactic acid formation, and subjected to IRL (50 cmH2O.l-1.s) for 120 min followed by naloxone (NLX; 0.3 mg/kg iv). Electromyographic activities of the diaphragm (EMGdi), external oblique (EMGeo), and external intercostal (EMGei) were measured and expressed as a percentage of activity at an end-tidal CO2 of 8%. DCA blocked the NLX-induced augmentation of all EMGs observed after 120 min of IRL as follows (means +/- SE): delta EMGdi from 20.8 +/- 5.6% (saline) to 1.2 +/- 2.7% (DCA), delta EMGeo from 116.6 +/- 30.9% (saline) to 5.3 +/- 11.4% (DCA), and delta EMGei from 43.8 +/- 11.3% (saline) to -4.5 +/- 5.6% (DCA) (all P less than 0.05, DCA vs. saline). We conclude that lactic acid produced by the contracting respiratory muscles is the stimulus responsible for endogenous opioid pathway activation during IRL.