Document Detail


Opioids contribute to hypoxia-induced pial artery dilation through activation of ATP-sensitive K+ channels.
MedLine Citation:
PMID:  7573545     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
V Shankar; W M Armstead
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  269     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-11-02     Completed Date:  1995-11-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H997-1002     Citation Subset:  IM    
Affiliation:
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / pharmacology*
Animals
Anoxia / physiopathology*
Blood Pressure
Blood Vessels / drug effects
Female
Glyburide / pharmacology
Male
Narcotics / pharmacology*
Pia Mater / blood supply*
Potassium Channels / drug effects,  physiology*
Receptors, Opioid / agonists
Swine
Vasodilation / physiology*
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Narcotics; 0/Potassium Channels; 0/Receptors, Opioid; 0/Vasodilator Agents; 10238-21-8/Glyburide; 56-65-5/Adenosine Triphosphate

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