Circulation, Vol 83, 652-660, Copyright © 1991 by American Heart Association
H Shimokawa, NA Flavahan and PM Vanhoutte
Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits
endothelium-dependent relaxations to certain agonists in porcine coronary
arteries. In the present study, the effects of the toxin were examined on
endothelium-dependent and -independent relaxations of hypercholesterolemic
and atherosclerotic porcine coronary arteries to assess the functional
state of the endothelial pertussis toxin- sensitive G protein. Male
Yorkshire pigs were maintained on either a regular diet (control group, n =
7) or a 2% high-cholesterol diet (cholesterol-fed group, n = 7) for 10
weeks. After the initial 2 weeks of maintenance, animals in both groups
underwent balloon catheter removal of the endothelium of the left anterior
descending or left circumflex coronary arteries. Endothelium-dependent
responses were examined in vitro after 10 weeks of maintenance; at this
time, a full lining of endothelial cells in both left coronary arteries was
confirmed histologically. In arteries with endothelium of the control group
(normal responses), pertussis toxin significantly inhibited the
endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha
2-adrenergic receptor agonist), and thrombin but not those to ADP,
bradykinin, or the calcium ionophore A23187. In previously denuded arteries
of the control group (effects of endothelial regeneration alone) or intact
arteries of the cholesterol-fed group (effects of hypercholesterolemia
alone), the relaxations to serotonin, UK14304, and thrombin were impaired
significantly; those relaxations were impaired further in previously
denuded arteries of the cholesterol-fed group (effects of atherosclerosis).
The inhibitory effects of pertussis toxin were significantly reduced after
endothelial regeneration and in hypercholesterolemia and were almost absent
in atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
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