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 (KATP) 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 KATP 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 PO2 approximately 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 KATP 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 KATP contributes to methionine enkephalin- and leucine enkephalin-induced dilation. Furthermore, these observations suggest that opioids contribute to hypoxia-induced pial artery dilation via KATP activation.
Shankar
V
V
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
Armstead
W M
WM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000819:agonists; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D009294:Narcotics; D015221:Potassium Channels; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D005905:Glyburide