Enhanced synthesis of epoxyeicosatrienoic acids by cholesterol-fed rabbit aorta. Am J Physiol 1991 Sep;261(3 Pt 2):H843-52
Date
09/01/1991Pubmed ID
1887929DOI
10.1152/ajpheart.1991.261.3.H843Scopus ID
2-s2.0-0025944931 (requires institutional sign-in at Scopus site) 94 CitationsAbstract
Arachidonic acid metabolism via cyclooxygenase, lipoxygenase, and cytochrome P-450 epoxygenase was investigated in thoracic aortic tissue obtained from rabbits fed either standard rabbit chow or chow containing 2% cholesterol. Aortic strips were incubated with [14C]arachidonic acid and A23187. Metabolites from extracted media were resolved by high-pressure liquid chromatography (HPLC). Normal and cholesterol-fed rabbit aortas synthesized prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs). The major cyclooxygenase products were 6-keto-PGF1 alpha and PGE2. Basal aortic 6-keto-PGF1 alpha production was slightly reduced in cholesterol-fed compared with normal rabbits. 12(S)- and 15(S)-HETE were the major aortic lipoxygenase products from both normal and cholesterol-fed rabbits. The structures were confirmed by gas chromatography-mass spectrometry (GC-MS). Only cholesterol-fed rabbit aortas metabolized arachidonic acid via cytochrome P-450 epoxygenase to the epoxyeicosatrienoic acids (EETs). 14,15-, 11,12-, 8,9-, and 5,6-EET were identified based on comigration on HPLC with known 14C-labeled standards and typical mass spectra. Incubation of normal aorta with 14,15-EET decreased the basal synthesis of 6-keto-PGF1 alpha. The other EETs were without effect. The four EET regioisomers relaxed the norepinephrine-precontracted normal and cholesterol-fed rabbit aorta. The relaxation response to 14,15-EET was greater in aortas from cholesterol-fed rabbits. These studies demonstrate that hypercholesterolemia, before the development of atherosclerosis, alters arachidonic acid metabolism via both the cyclooxygenase and epoxygenase pathways.
Author List
Pfister SL, Falck JR, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinSandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
6-Ketoprostaglandin F1 alpha
8,11,14-Eicosatrienoic Acid
Animals
Aorta, Thoracic
Arachidonic Acids
Carbon Radioisotopes
Cholesterol, Dietary
Clotrimazole
Diet, Atherogenic
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Indomethacin
Kinetics
Masoprocol
Metyrapone
Muscle, Smooth, Vascular
Rabbits
Reference Values
Stereoisomerism
