Vascular responses to activated leukocytes after regression of atherosclerosis.
Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)
Padgett
R C
RC
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA.
Heistad
D D
DD
Mügge
A
A
Armstrong
M L
ML
Piegors
D J
DJ
Lopez
J A
JA
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D008055:Lipids; D012701:Serotonin; D009240:N-Formylmethionine Leucyl-Phenylalanine