Evaluation of chemical mediator-induced respiratory center inhibition in medulla

用阿片（μ-、κ-和δ-受体激动剂）、细胞因子（tnf - α）和非甾体抗炎药（水杨酸）对新生大鼠离体脑干-脊髓制备物的吻侧腹外侧髓质（RVLM）吸气神经元的膜电位和阻力（Rm）进行了测定。μ-和κ-阿片受体激动剂主要通过抑制髓质吸气神经元网络导致最终运动输出减少。这种对吸气神经元的抑制似乎是由于突触前和突触后的抑制。由吸气前神经元爆发率反映的中枢呼吸节律基本上未被激动剂改变。tnf - α诱导呼吸抑制。静息膜电位超极化，Rm降低。这些结果表明，tnf - α诱导的呼吸抑制似乎是突触后的作用。低剂量水杨酸增加吸气神经元破裂。大剂量水杨酸可降低大鼠呼吸神经元的爆发率。而10mm水杨酸盐的抑制作用被GABA受体拮抗剂所拮抗。静息膜电位没有变化。水杨酸对髓质吸气神经元的作用似乎是由于突触前效应。gaba能机制可能参与水杨酸诱导的中枢呼吸抑制。

Membrane potential and resistance (Rm) were measured in inspiratory neurons in rostral ventrolateral medulla (RVLM) of the isolated brainstem - spinal cord preparation from newborn rats during bath application of opioids (μ-,κ-, and δ- receptor agonists), cytokine (TNF-alfa), and NSAID (salicylate).μ-andκ-opioid receptor agonists caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be due to both a pre - and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists.TNF-alfa induced respiratory depression. Resting membrane potential hyperpolarized and Rm decreased. These results mean that TNF-alfa-induced respiratory depression seems to be a postsynaptic action.Low dose salicylate increased in inspiratory neuron burst. While the burst rates of inspiratory neuron were decreased after application of high dose salicylate. While the depressant effects by 10 mM salicylate were antagonized by GABA receptor antagonist. Resting membrane potential did not change. Salicylate effects on the medullary inspiratory neurons seem to be due to presynaptic effect. GABAergic mechanisms are probably involved in the salicylate-induced central respiratory depression.