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COX‐1 and COX‐2 differentially regulate vascular tone in mouse mesenteric artery
Author(s) -
Zhou Yingbi,
Flavahan Sheila,
Flavahan Nicholas A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a495-b
Subject(s) - phenylephrine , contraction (grammar) , mesenteric arteries , chemistry , cyclooxygenase , endocrinology , celecoxib , vasodilation , arachidonic acid , medicine , acetylcholine , myograph , artery , biochemistry , enzyme , blood pressure
NO‐independent, endothelium‐derived mediators are important regulators of vascular tone. The goal of this study was to determine how arachidonic acid (AA) metabolism through cyclooxygenase‐1 (COX‐1) and COX‐2 isoforms regulates vasoreactivity in mouse mesenteric arteries, in the absence of NO activity. Arterial rings were suspended for isometric contraction in the presence of the NO synthase inhibitor, Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 1 mM). In arteries contracted with the α1‐adrenergic agonist phenylephrine, AA (10 to 300 μM) caused relaxation, which was inhibited by the non‐selective COX inhibitor indomethacin (3 μM) or the selective COX‐1 inhibitor SC‐560 (0. 3 μM). In a similar manner, acetylcholine (0.1 to 100 μM) caused relaxation of phenylephrine‐induced contraction which was reduced by indomethacin or SC‐560. In contrast, AA‐induced relaxation was increased by the selective COX‐2 inhibitor celecoxib (1 μM). Celecoxib did not affect relaxation to acetylcholine. After endothelial‐denudation, AA (10 to 300 μM) increased phenylephrine‐induced contraction and this amplification was inhibited by celecoxib. These results suggest that endothelial COX‐1‐derived AA metabolites contribute to NO‐independent relaxation, whereas COX‐2‐derived metabolites, which are likely generated by the smooth muscle, counter this dilator activity.