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Effect of celecoxib on cyclooxygenase-1-mediated prostacyclin synthesis and endothelium-dependent contraction in mouse arteries.
MedLine Citation:
PMID:  23127498     Owner:  NLM     Status:  Publisher    
This study aimed to determine whether a cyclooxygenase-2 (COX-2) inhibitor celecoxib influences endothelium-dependent contraction independent of its action on COX-2 and, if so, the underlying mechanism(s). Abdominal aortas and/or carotid arteries from C57BL/6 mice or those with genetic COX-2 deficiency (COX-2(-/-)) were isolated for functional and/or biochemical analyses. Result showed that following NO synthase inhibition celecoxib not only reduced the contraction evoked by acetylcholine in C57BL/6 abdominal aorta, but also that in COX-2(-/-) mice showing a comparable magnitude. Notably, the IC(50) of celecoxib obtained in COX-2(-/-) abdominal aorta was only ~0.364μM. Also, celecoxib exhibited a similar effect on COX-2(-/-) carotid arteries. Interestingly, celecoxib was not only found to inhibit the production of the prostacyclin (PGI(2)) metabolite 6-keto-PGF(1α) in COX-2(-/-) aortas, but also caused a reduction in the contraction evoked by PGI(2), by the α(1)-adrenergic agonist phenylephrine, or by 30mM K(+)-induced depolarization in COX-2(-/-) and/or C57BL/6 abdominal aorta. Moreover, N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS398), another COX-2 inhibitor, also reduced the contraction evoked by acetylcholine or by 30mM K(+)-induced depolarization in COX-2(-/-) mice. These results demonstrate explicitly that in mouse arteries celecoxib not only inhibits COX-1-mediated synthesis of PGI(2) and probably some other prostanoids, but also causes a reduction in vessel contractility that is independent of either COX-2 or COX-1, leading to an inhibition of COX-1-mediated endothelium-dependent contraction with an IC(50) value far below that of it considered for COX-1. Also, our data suggest that such effects of celecoxib could be possibly shared by some other COX-2 inhibitors, such as NS398.
Bin Liu; Wenhong Luo; Yingzhan Zhang; Hui Li; Ningxia Zhu; Dongyang Huang; Yingbi Zhou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-2
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Cardiovascular Research Center, Shantou University Medical College, Shantou, China.
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