Opioids contribute to hypoxia-induced pial artery dilation through
activation of atp-sensitive k+ channels.
Shankar, V., and W. M. Armstead.
Departments of Anesthesia and Pharmacology, The University of
Pennsylvania and the Children's Hospital of Philadelphia,
Philadelphia, PA 19104
APStracts 2:0143H, 1995.
It has been previously observed that hypoxia increases 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 (10-6M),
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 (PaO2 nearly equal to 35 mmHg and 25 mmHg
respectively) in the absence vs presence of glibenclamide]. In
addition, glibenclamide attenuated the dilation produced by
methionine enkephalin (10-8, 10-6M) (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 (10-8,10-6M) 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. Further, these observations
suggest that opioids contribute to hypoxia-induced pial artery
dilation via KATP activation.
Received 15 January 1995; accepted in final form 30 March 1995.
APS Manuscript Number H68-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.