Increased prostacyclin and thromboxane A sub 2 biosynthesis in atherosclerosis

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.12.4511· OSTI ID:5563145

Mehta, J L; Lawson, D; Mehta, P; Saldeen, T ^[1]

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1. Univ. of Florida, Gainesville (USA)

It has been proposed that atherosclerotic arteries produce less prostacyclin (PGI{sub 2}) than nonatherosclerotic arteries do, thereby predisposing arteries to vasospasm and thrombosis in vivo. The authors reexamined this concept by measuring spontaneous as well as arachidonate-induced PGI{sub 2} biosynthesis in aortic segments from nonatherosclerotic and cholesterol-fed atherosclerotic New Zealand White rabbits. Thromboxane A{sub 2} (TXA{sub 2}) generation was also measured. Formation of PGI{sub 2}, as well as TXA{sub 2}, as measured by radioimmunoassay (RIA) of their metabolites, was increased in atherosclerotic aortic segments relative to nonatherosclerotic segments at 0, 5, 10, 15 and 30 min of incubation with arachidonate. Pretreatment of arterial segments with indomethacin inhibited PGI{sub 2} as well as TXA{sub 2} formation, whereas pretreatment with the selective TXA{sub 2} inhibitor OKY-046 inhibited only TXA{sub 2} release, thus confirming the identity of icosanoids. To confirm the RIA data, aortic segments were incubated with ({sup 14}C)arachidonate prior to stimulation with unlabeled arachidonate. The uptake of arachidonate was similar, but the release of incorporated ({sup 14}C)arachidonate was significantly greater in atherosclerotic segments than in nonatherosclertic ones. Thus, synthesis of PGI{sub 2} as well as TXA{sub 2} is increased in atherosclerosis, and this alteration in arachidonate metabolism is related to increased release of arachidonate.

• OSTI ID: 5563145
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:12; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
AORTA
ARACHIDONIC ACID
ARTERIES
ARTERIOSCLEROSIS
BIOASSAY
BIOSYNTHESIS
BLOOD VESSELS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
DIAGNOSTIC TECHNIQUES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
ETIOLOGY
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROSTAGLANDINS
RABBITS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
SYNTHESIS
TRACER TECHNIQUES
UPTAKE
VASCULAR DISEASES
VERTEBRATES