Armstead W M
Departments of Anesthesia and Pharmacology, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Am J Physiol. 1998 Sep;275(3):H861-7. doi: 10.1152/ajpheart.1998.275.3.H861.
Because methionine enkephalin contributes to and dynorphin opposes dilation during a 10-min hypoxic exposure, opioids modulate pial artery dilation to this stimulus. However, such modulation may be dependent on the duration of hypoxia. The present study was designed to characterize the modulation of hypoxic pial dilation by opioids as a function of stimulus duration in newborn pigs equipped with a closed cranial window. Hypoxic dilation was decremented in both moderate and severe groups (PO2 approximately 35 and 25 mmHg, respectively) during 20-min and 40-min exposure periods compared with the response during 5 or 10 min of stimulation (24 +/- 1, 25 +/- 1, 18 +/- 1, and 14 +/- 1% for 5, 10, 20, and 40 min of moderate hypoxia; means +/- SE). Moderate and severe hypoxia had no effect on cerebral spinal fluid (CSF) methionine enkephalin or dynorphin concentration during a 5-min exposure period. During a 10-min exposure, however, both opioids were increased in CSF. During 20- and 40-min exposure periods, CSF dynorphin continued to increase, whereas methionine enkephalin steadily decreased (962 +/- 18, 952 +/- 21, 2,821 +/- 15, 2,000 +/- 81, and 1,726 +/- 58 pg/ml methionine enkephalin for control, 5, 10, 20, and 40 min of moderate hypoxia, respectively). The mu-opioid (methionine enkephalin) antagonist beta-funaltrexamine had no influence on dilation during the 5-min exposure, decremented the 10- and 20-min exposures, but had no effect on 40-min exposure hypoxic dilation. Whereas the kappa-opioid (dynorphin) antagonist norbinaltorphimine similarly had no effect on a 5-min exposure dilation, it, in contrast, potentiated 10-, 20-, and 40-min exposure hypoxic dilations (23 +/- 1 vs. 23 +/- 1, 24 +/- 1 vs. 32 +/- 1, 16 +/- 1 vs. 24 +/- 2, and 13 +/- 1 vs. 23 +/- 3% for 5, 10, 20, and 40-min hypoxic dilation before and after norbinaltorphimine). These data show that opioids do not modulate hypoxic pial dilation during short but do so during longer exposure periods. Moreover, hypoxic pial dilation is diminished during longer exposure periods. Decremented hypoxic pial dilation during longer exposure periods results, at least in part, from decreased release of methionine enkephalin and accentuated release of dynorphin. These data suggest that the relative role of opioids in hypoxic pial dilation changes with the stimulus duration.
由于在10分钟的低氧暴露期间，甲硫氨酸脑啡肽促进软脑膜动脉扩张，而强啡肽则起相反作用，因此阿片类物质可调节软脑膜动脉对这种刺激的扩张反应。然而，这种调节可能取决于低氧持续时间。本研究旨在在配备闭合式颅骨视窗的新生仔猪中，将阿片类物质对低氧性软脑膜扩张的调节作用表征为刺激持续时间的函数。与5分钟或10分钟刺激期间的反应相比，在20分钟和40分钟暴露期内，中度和重度组（分别为PO2约35和25 mmHg）的低氧扩张均有所减少（中度低氧5、10、20和40分钟时分别为24±1、25±1、18±1和14±1%；均值±标准误）。在5分钟暴露期内，中度和重度低氧对脑脊液（CSF）中甲硫氨酸脑啡肽或强啡肽浓度没有影响。然而，在10分钟暴露期内，两种阿片类物质在脑脊液中均增加。在20分钟和40分钟暴露期内，脑脊液中的强啡肽持续增加，而甲硫氨酸脑啡肽则稳步下降（中度低氧对照组、5、10、20和40分钟时，甲硫氨酸脑啡肽分别为962±18、952±21、2821±15、2000±81和1726±58 pg/ml）。μ阿片类物质（甲硫氨酸脑啡肽）拮抗剂β-芬太尼酰苯丙胺在5分钟暴露期内对扩张没有影响，在10分钟和20分钟暴露期内使其减少，但对40分钟暴露期的低氧扩张没有影响。而κ阿片类物质（强啡肽）拮抗剂诺宾那托啡则同样对5分钟暴露期的扩张没有影响，相反，它增强了10分钟、20分钟和40分钟暴露期的低氧扩张（诺宾那托啡前后，5、10、20和40分钟低氧扩张分别为23±1对23±1、24±1对32±1、16±1对24±2和13±1对23±3%）。这些数据表明，阿片类物质在短时间内不调节低氧性软脑膜扩张，但在较长暴露期内会调节。此外，在较长暴露期内，低氧性软脑膜扩张会减弱。较长暴露期内低氧性软脑膜扩张减弱至少部分是由于甲硫氨酸脑啡肽释放减少和强啡肽释放增强所致。这些数据表明，阿片类物质在低氧性软脑膜扩张中的相对作用随刺激持续时间而变化。
