Effect of Endothelin-1 and Sarafotoxin S6b on Acute Platelet-Thrombus Formation in the Stenosed, Canine Coronary Artery
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Authors
Lee, Philmo
Issue Date
1992
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Endothelin-1 (ET-1), a recently discovered peptide produced by vascular
endothelial cells, may play a role in the complex process of intravascular
thrombus formation. The effect of ET-l or sarafotoxin S6b (a structural
analogue of ET-l) on acute platelet-thrombus formation was examined in the
stenosed canine coronary artery. A 70 - 80% stenosis was created by a plastic
obstructor placed around the vessel. Endothelial cell and intimal damage were
produced by compressing the vessel with vascular clamps. These conditions
induced platelets to aggregate at the stenosed region, causing coronary blood
flow to gradually decrease until it reached zero. At this point, the obstructor
was mechanically agitated, dislodging the thrombus and restoring flow. A new
platelet-thrombus then formed at the stenosed area, and the previous cycle was
repeated. This repetitive flow pattern is referred to as cyclic flow reductions
(CFRs). ET-1 and S6b (0.5 µg/kg, i.v. bolus) inhibited the development of an
occlusive platelet-thrombus, as indicated by inhibition of CFRs. In addition,
ET-l and S6b inhibited platelet-thrombus formation in dogs pretreated with
aspirin (5 mg/kg), an inhibitor of prostacyclin (PGI2) production. PGI2 is a
potent antiaggregatory agent also derived from the vascular endothelium. ET-
1 and S6b possess antithrombotic activity in vivo that is not due to the
secondary release of PGI2. It is possible that the antithrombotic effects of ET-l
demonstrated in this model may be due to a direct action of ET-l on platelets,
or to endothelin-mediated release of other antiaggregtory factors.
With honors.
With honors.
Description
v, 41 p.
Citation
Publisher
Kalamazoo College
License
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