Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.15.5893· OSTI ID:6791079

Catella, F; Lawson, J A; Fitzgerald, D J; FitzGerald, G A ^[1]

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1. Vanderbilt Univ., Nashville, TN (USA)

Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension.

• OSTI ID: 6791079
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:15; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
METABOLISM
EICOSANOIC ACID
BIOSYNTHESIS
HYPERTENSION
PATHOGENESIS
BIOLOGICAL HALF-LIFE
DOGS
ISOENZYMES
MAN
METABOLITES
PREGNANCY
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
DISEASES
ISOTOPE APPLICATIONS
MAMMALS
MATERIALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
SYMPTOMS
SYNTHESIS
VASCULAR DISEASES
VERTEBRATES
WASTES
550901* - Pathology- Tracer Techniques