Vascular Responses to Leukocyte Products in Atherosclerotic Primates

Little is known about the possible role of leukocytes in the pathogenesis of vasospasm. We hypothesized that vasoactive products released by leukocytes might produce constriction of atherosclerotic arteries. To test this hypothesis, we infused fmet-leu-phe (fMLP), a peptide that activates leukocytes...

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Bibliographic Details
Published in:Circulation research 1989-10, Vol.65 (4), p.1078-1086
Main Authors: Lopez, J Antonio G, Armstrong, Mark L, Harrison, David G, Piegors, Donald J, Heistad, Donald D
Format: Article
Language:English
Subjects:
Animals
Arteries - drug effects
Arteries - physiopathology
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Arteriosclerosis - physiopathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Dinoprostone - pharmacology
Epoprostenol - pharmacology
Hemodynamics
Leukocyte Count
Leukocytes - metabolism
Lipids - blood
Macaca fascicularis
Male
Medical sciences
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Platelet Activating Factor - pharmacology
SRS-A - pharmacology
Vasoconstrictor Agents - metabolism
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Summary:Little is known about the possible role of leukocytes in the pathogenesis of vasospasm. We hypothesized that vasoactive products released by leukocytes might produce constriction of atherosclerotic arteries. To test this hypothesis, we infused fmet-leu-phe (fMLP), a peptide that activates leukocytes to release their vasoactive products, into the perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Infusion of fMLP did not change resistance of large arteries in normal monkeys. In contrast, fMLP produced pronounced constriction of large arteries in atherosclerotic monkeys. To determine whether leukotrienes, platelet-activating factor, or prostaglandin E2 (PGEJ2 which are released by leukocytes, may contribute to leukocyte-induced vasoconstriction in atherosclerotic monkeys, we injected leukotriene D49 platelet-activating factor, and PGE2 intra-arterially into the perfused hind limb. Leukotriene D4 and platelet-activating factor had minimal effects on large arteries in both normal and atherosclerotic monkeys. PGE2 produced marked constriction of large arteries in atherosclerotic, but not normal, monkeys. Thus, pronounced constriction in atherosclerotic, but not normal, arteries during infusion of fMLP suggests that products released by leukocytes may mediate vasoconstriction in atherosclerotic vessels. Vasoconstrictor responses to PGE2 are profoundly potentiated by atherosclerosis, which suggests that PGE2 may contribute to leukocyte-induced vasoconstriction.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.65.4.1078