Platelet-activating factor attenuates endothelium-dependent
coronary arteriolar vasodilation.
Defily, David V., Lih Kuo, and William M. Chilian.
Department of Medical Physiology & Microcirculation Research
Institute, Texas A & M University Health Science Center, College
Station, TX 77843-1114
APStracts 2:0512H, 1995.
Platelet-activating factor (PAF) has been reported to play a role in
neutrophil activation, microvascular permeability and endothelial
dysfunction in a variety of microvascular and large vessel
preparations. It is not known, however, whether the deleterious
effects of PAF also extend to coronary resistance vessels. Also,
although a majority of PAFs effects are thought to be mediated by the
activation of neutrophils, it is unclear the extent to which
activated neutrophils cause injury to coronary arterioles. Therefore,
the purpose of this study was to determine whether PAF causes
coronary arteriolar endothelial dysfunction in vivo. Furthermore, we
also tested the hypothesis that PAF-induces dysfunction of coronary
arteriolar endothelium independent of activated neutrophils. To test
these hypotheses, we measured changes in coronary arteriolar diameter
to endothelium-dependent and -independent dilators in vivo by
measuring coronary microvascular diameters in a beating canine heart
using intravital video-microscopy with fluorescent stroboscopic epi
-illumination following intracoronary infusion of PAF (20 ng/kg x
min). Changes in coronary arteriolar diameter following incubation
with PAF were also measured in isolated coronary arterioles. In vivo,
incubation with PAF resulted in a significant attenuation of
endothelium-dependent dilation to intracoronary acetylcholine (0.1
[mu]g/kg x min, 39+/-7% vs. 20+/-3% dilation) and serotonin
(1[mu]g/kg x min, 29+/-6 vs. 2+/-2% dilation). Papaverine induced
relaxation however, was unchanged (41+/-5% vs. 40+/-4%). Likewise, in
vitro, relaxation to serotonin (10 nM) was significantly reduced
(38+/-4% vs. 3+/-5%) following treatment with PAF, whereas,
nitroprusside (10 nM) induced relaxation, was unchanged (20+/-7% vs.
22+/-6%). Because PAF impaired endothelium-dependent arteriolar
dilation both in vivo and in vitro, we conclude that the presence of
activated neutrophils are not required for PAF-induced coronary
microvascular dysfunction.
Received 29 June 1995; accepted in final form 7 November 1995.
APS Manuscript Number H600-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95