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Morphological and functional changes of coronary vasculature caused by
transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart
of rabbit
A Sala, GM Aliev, G Rossoni, F Berti, C Buccellati, G Burnstock, G Folco and J Maclouf
Center for Cardiopulmonary Pharmacology, University of Milan, Italy.
Morphological and functional modifications occurring in Langendorff rabbit
heart preparations perfused with purified human leukocytes (PMNL), as an
organ model of sulfidopeptide-leukotrienes (sLT) transcellular
biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as
an index of coronary vasospasm, increased by 295% after challenge with the
Ca(2+)-ionophore A-23187 (0.5 micromol/L) for 30', accompanied by a
significant formation of sLT. Increase in CPP was prevented by PMNL
pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 micromol/L) or by
heart pretreatment with LTD4-receptor antagonist SKF 104353, indicating a
pivotal role of PMNL-derived 5-lipoxygenase (5- LO) products in the
observed functional modifications. Similar effects were obtained using
granulocyte macrophage-colony stimulating factor- primed PMNL challenged
with the tripeptide n-formyl-methionyl-leucyl- phenylalanine. Scanning
electron microscopy (SEM) of coronary arteries showed craters on the vessel
luminal surface, PMNL adhering to endothelial cells (EC), increased number
of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM
and transmission electron microscopy of myocardial microvessels, showed
presence of perivascular and intermuscle edema, presence of activated PMNL
and decreased number of patent microvessels. These morphological
alterations were significantly blunted by MK-886 or SKF 104353. These data
provide evidence of close interaction between PMNL and myocardial EC,
resulting in enhanced sLT formation via transcellular biosynthesis,
originating from transfer of PMNL-derived LTA4 to EC. These potent
proinflammatory autacoids are responsible for coronary vasospasm and the
morphological alternations observed.
Volume 87,
Issue 5,
pp. 1824-1832,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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