ROLE OF OPIOIDS IN HYPOXIC PIAL ARTERY DILATION IS STIMULUS-DURATION DEPENDENT

Because methionine enkephalin contributes to and dynorphin apposes dil ation during a 10-min hypoxic exposure, opioids modulate pial artery d ilation to this stimulus. However, such modulation may be dependent on the duration of hypoxia. The present study was designed to characteri ze the modulation of hypoxic pial dilation by opioids as a function of stimulus duration in newborn pigs equipped with a closed cranial wind ow. Hypoxic dilation was decremented in both moderate and severe group s (Po-2 approximate to 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 seve re hypoxia had no effect on cerebral spinal fluid (CSF) methionine enk ephalin or dynorphin concentration during a 5-min exposure period. Dur ing a 10-min exposure, however, both opioids were increased in CSF. Du ring 20- and 40-min exposure periods, CSF dynorphin continued to incre ase, 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, re spectively). The mu-opioid (methionine enkephalin) antagonist beta-fun altrexamine had no influence on dilation during the 5-min exposure, de cremented the 10- and 20-min exposures, but had no effect on M-min exp osure hypoxic dilation. Whereas the K-opioid (dynorphin) antagonist no rbinaltorphimine similarly had no effect on a Ei-min exposure dilation , it, in contrast, potentiated 10-, 20-, and 40-min exposure hypoxic d ilations (23 +/- 1 vs. 23 +/- 1, 24 +/- 1 vs. 32 +/- 1, 16 +/- 1 vs. 2 4 +/- 2, and 13 +/- 1 vs. 23 +/- 3% far 5, 10, 20, and 40-min hypoxic dilation before and after norbinaltorphimine). These data show that op ioids do not modulate hypoxic pial dilation during short but do so dur ing longer exposure periods. Moreover, hypoxic pial dilation is dimini shed during longer exposure periods. Decremented hypoxic pial dilation during longer exposure periods results, at least in part, from decrea sed release of methionine enkephalin and accentuated release of dynorp hin. These data suggest that the relative role of opioids in hypoxic p ial dilation changes with the stimulus duration.