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Cyclo‐oxygenase‐1 or ‐2‐mediated metabolism of arachidonic acid in endothelium‐dependent contraction of mouse arteries
Author(s) -
Zhou Yingbi,
Luo Wenhong,
Zhang Yingzhan,
Li Hui,
Huang Dongyang,
Liu Bin
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.072017
Subject(s) - prostacyclin , prostaglandin h2 , endothelium , contraction (grammar) , arachidonic acid , prostanoid , prostaglandin , medicine , endocrinology , thromboxane a2 , chemistry , hydroxyeicosatetraenoic acid , biology , biochemistry , platelet , enzyme
New findings• What is the central question of this study? To determine the specific cyclo‐oxygenase (COX) isoform(s) involved in endothelium‐dependent contraction and whether prostaglandin I 2 , a mediator of endothelium‐derived vasoconstrictor activity, can be generated in medial smooth muscle from prostaglandin H 2 that might diffuse from the endothelium. • What is the main finding and its importance? Our results demonstrate a predominant role for COX‐1 in arachidonic acid metabolism and suggest that in the given mouse arteries, metabolites from either COX isoform cause contraction. Moreover, our results imply that some of the prostaglandin I 2 involved in the vasoconstrictor activity of endothelial COX‐mediated metabolism could possibly be generated from prostaglandin H 2 in the medial smooth muscle. These findings add to our current understanding of mechanisms for endothelium‐dependent contraction.This study aimed to determine whether the cyclo‐oxygenase (COX) substrate arachidonic acid (AA) evokes endothelium‐dependent contraction and, if so, the specific COX isoform(s) involved and whether prostacyclin (prostaglandin I 2 ; PGI 2 ), a mediator of endothelium‐derived vasoconstrictor activity, can be generated in medial smooth muscle from the intermediate COX product prostaglandin H 2 (PGH 2 ) that might diffuse from the endothelium. Aortae and/or carotid arteries were isolated from C57BL/6 mice or those lacking one of the two COX isoforms (COX‐1 −/− or COX‐2 −/− ) for functional and/or biochemical analyses. Results showed that in vessels from C57BL/6 mice, exogenous AA evoked not only endothelium‐dependent production of the PGI 2 metabolite 6‐keto‐PGF 1α , but also contractions reduced by thromboxane–prostanoid receptor antagonism or endothelial denudation. The minimal concentration for AA to evoke contraction was 0.3 μ m , a level thought to activate only COX‐2. However, neither the contraction nor 6‐keto‐PGF 1α production was altered in vessels from COX‐2 −/− mice, while both were reduced in COX‐1 −/− counterparts. In vessels from COX‐1 −/− mice, AA also caused minor contractions that were sensitive to non‐selective COX inhibition. Real‐time PCR showed that like COX‐1, COX‐2 mainly existed in the endothelium, but it was unaltered in COX‐1 −/− mice. Also, we noted that in endothelium‐denuded aortae, PGH 2 generated PGI 2 as in intact vessels. These results demonstrate a predominant role for COX‐1 and suggest that in the given mouse arteries, metabolites from either COX isoform cause contraction. Moreover, our results imply that some of the PGI 2 involved in vasoconstrictor activity of endothelial COX‐mediated metabolism could possibly be generated from PGH 2 in medial smooth muscle.