OPIOIDS CONTRIBUTE TO HYPOXIA-INDUCED PIAL ARTERY DILATION THROUGH ACTIVATION OF ATP-SENSITIVE K+ CHANNELS

It has been previously observed that hypoxia increases cerebrospinal fluid (CSF) methionine enkephalin and leucine enkephalin levels, and these opioids contribute to hypoxia-induced pial artery vasodilation. The present study was designed to investigate whether the activation of ATP-sensitive K+ channels (K-ATP) mediates the contribution of opioids to the hypoxia-induced pial artery dilation. The closed-cranial window technique was used to measure pial diameter in newborn pigs. Glibenclamide (10(-6) M), a K-ATP inhibitor, attenuated the dilation resulting from moderate and severe hypoxia [23 +/- 1 and 33 +/- 2% vs. 7 +/- 1 and 18 +/- 2%, respectively, for moderate and severe hypoxia (arterial Po-2 approximate to 35 and 25 mmHg, respectively) in the absence vs. presence of glibenclamide]. In addition, glibenclamide attenuated the dilation produced by methionine enkephalin (10(-8) and 10(-6) M) (13 +/- 1 vs. 4 +/- 2% and 21 +/- 2 vs. 7 +/- 3%, respectively, for methionine enkephalin in the absence and presence of glibenclamide). Leucine enkephalin-induced dilation was similarly attenuated by glibenclamide. Cromakalim (10(-8) and 10(-6) M), a K-ATP agonist, produced dilation that was blocked by glibenclamide (12 +/- 1 and 25 +/- 1 vs. 3 +/- 1 and 5 +/- 1% before and after glibenclamide, respectively). These data show that activation of K-ATP contributes to methionine enkephalin- and leucine enkephalin-induced dilation. Furthermore, these observations suggest that opioids contribute to hypoxia-induced pial artery dilation via K-ATP activation.