Document Detail


Involvement of Cyclooxygenase-1 Mediated Prostacyclin Synthesis in the Vasoconstrictor Activity Evoked by ACh in Mouse Arteries.
MedLine Citation:
PMID:  22080487     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI(2)), and if so, to determine how PGI(2) affects vasomotor reactivity and whether cyclooxygenase-1 (COX-1) contributes to PGI(2) synthesis. Abdominal aortas, carotid and femoral arteries were isolated from wild-type mice and/or those with COX-1 or -2 deficiency (COX-1(-/-); COX-2(-/-)) for biochemical and/or functional analyses. The PGI(2) metabolite 6-keto-PGF(1α) was analyzed with High Performance Liquid Chromatography-Mass Spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta ACh evoked endothelium-dependent production of 6-keto-PGF(1α), which was abolished by COX-1(-/-), but not by COX-2(-/-). Interestingly, COX-1(-/-) enhanced the dilation to ACh, while PGI(2), which evoked relaxation of the mesenteric artery, caused contraction that was abolished by antagonizing thromboxane-prostanoid (TP) receptors in the abdominal aorta. However, the TP receptor agonist U46619 evoked similar contractions in the abdominal aorta and mesenteric artery. Also, antagonizing TP receptors enhanced the relaxation to PGI(2) in mesenteric arteries. Real-time PCR showed that PGI(2) (IP) receptor mRNA level was lower in the abdominal aorta than in mesenteric arteries. In addition, COX-1(-/-) not only abolished the contraction to ACh following NO inhibition in abdominal aorta, but also those in the carotid and femoral arteries. These results demonstrate an explicit role for endothelial COX-1 in PGI(2) synthesis, and suggested that in given mouse arteries PGI(2) mediates not dilation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI(2) to act mainly on TP receptors.
Authors:
Bin Liu; Wenhong Luo; Yingzhan Zhang; Hui Li; Ningxia Zhu; Dongyang Huang; Yingbi Zhou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-11
Journal Detail:
Title:  Experimental physiology     Volume:  -     ISSN:  1469-445X     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Shantou University College of Medicine;
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