Influence of stimulation train length on the opioid-induced inhibition of norepinephrine release in the rabbit ear artery.

Influence of stimulation train length on the opioid-induced inhibition of norepinephrine release in the rabbit ear artery.
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刺激序列长度对阿片类药物诱导的兔耳动脉去甲肾上腺素释放抑制的影响。

DOI:
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发表时间:
1988
影响因子:
3.5
通讯作者:
S. Duckles
S. Duckles
中科院分区:
医学2区
文献类型:
--
作者:
D. Budai;S. Duckles

文献摘要

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在兔耳动脉灌注段,比较阿片激动剂对肾上腺素能神经刺激和刺激诱发的[3H]去甲肾上腺素溢出血管收缩反应的影响,采用8、40或120组8 Hz、持续时间为1毫秒、振幅为40 V的单相脉冲。两种选择性肽[D-Ala2, D-Leu5]-脑啡肽、-脑啡肽和-脑啡肽,以及优先的kappa配体dynorphin1-13和乙基酮环唑辛,均能显著降低8 Hz脉冲引起的血管收缩。这种效应的大小与刺激序列的长度成反比。在大多数情况下,阿片类激动剂在短脉冲刺激下非常有效,但在120脉冲8赫兹的刺激下,不能使血管收缩反应降低10%至15%以上。与这些数据良好相关的是,在用[3H]去甲肾上腺素预培养的组织中,阿片类药物对8或120次8 Hz脉冲诱发的氚溢出的抑制作用与刺激长度成反比。我们的研究结果证实,阿片激动剂与异质的结前受体群体相互作用,调节兔离体耳动脉中动作电位诱发的去甲肾上腺素释放。这种调节在刺激训练开始时更为明显,此时去甲肾上腺素释放的负反馈抑制仍未完全起作用。这表明,阿片肽的生理作用可能在短时间血管收缩而不是长时间血管收缩期间更为显著。
In perfused segments of rabbit ear artery the effects of opioid agonists on vasoconstrictor responses to adrenergic nerve stimulation and stimulation-evoked [3H]norepinephrine overflow were compared using trains of 8, 40 or 120 monophasic pulses at 8 Hz with 1 msec duration and 40 V amplitude. Both delta selective peptides, [D-Ala2, D-Leu5]-enkephalin, met-enkephalin and leu-enkephalin, and preferential kappa ligands, dynorphin1-13 and ethylketocyclazocine, significantly reduced the vasoconstriction evoked by 8 pulses at 8 Hz. The magnitude of this effect was inversely related to the stimulus train length. In most cases, opioid agonists were highly effective with short stimulus trains, but failed to decrease vasoconstrictor responses by more than 10 to 15% with trains of 120 pulses at 8 Hz. In good correlation with these data, in tissue preincubated with [3H]norepinephrine the inhibitory effect of opioids on the tritium overflow evoked by 8 or 120 pulses at 8 Hz was inversely proportional to the length of stimulation. Our findings confirm that opioid agonists interact with a heterogeneous prejunctional receptor population to modulate the action potential-evoked release of norepinephrine in the isolated ear artery of the rabbit. This modulation is more pronounced at the beginning of a stimulus train when the negative feedback inhibition of norepinephrine release is still not fully operative. It is suggested that the physiological role of opioid peptides could be more significant during a short rather than a prolonged vasoconstriction.