© 1999 American Heart Association, Inc.
Original Contribution |
Alteration of Endothelium-Dependent Hyperpolarizations in Porcine Coronary Arteries With Regenerated Endothelium
From the Institut de Recherches Servier, Suresnes, France.
Correspondence to Catherine Thollon, PhD, Institut de Recherches Servier, Division pathologies cardiaques et vasculaires, 11 rue des Moulineaux, 92150 Suresnes, France.
Abstract—The present
study was designed to test the ability of regenerated
endothelium to evoke
endothelium-dependent
hyperpolarizations.
Hyperpolarizations induced by serotonin
and bradykinin were compared in isolated porcine coronary
arteries with native or regenerated endothelium, 4
weeks after balloon endothelial denudation. The
experiments were performed in the presence of inhibitors of
nitric oxide synthase
(N
-nitro-L-arginine) and
cyclooxygenase (indomethacin). The
transmembrane potential was measured using conventional glass
microelectrodes. Smooth muscle cells from coronary arteries
with regenerated endothelium were depolarized in
comparison with control coronary arteries from the same hearts.
Spontaneous membrane potential oscillations of small
amplitude or spikes were observed in some of these arteries but never
in arteries with native endothelium. In
coronary arteries from control pigs, both serotonin
and bradykinin induced concentration-dependent
hyperpolarizations. In the presence of ketanserin,
10 µmol/L serotonin induced a transient
hyperpolarization in control coronary
arteries. Four weeks after balloon denudation, the response to
serotonin was normal in arteries with native
endothelium, but the
hyperpolarization was significantly lower in
coronary arteries with regenerated endothelium.
In control arteries, the endothelium-dependent
hyperpolarization obtained with bradykinin (30
nmol/L) was reproducible. Four weeks after balloon denudation,
comparable hyperpolarizations were obtained in
coronary arteries with native endothelium. By
contrast, in arteries with regenerated endothelium, the
hyperpolarization to bradykinin became
voltage-dependent. In the most depolarized cells, the
hyperpolarization to bradykinin was augmented. The
changes in resting membrane potential and the alteration in
endothelium-dependent
hyperpolarizations observed in the coronary
arteries with regenerated endothelium may contribute to
the reduced response to serotonin and the unchanged
relaxation to bradykinin described previously.
Key Words: regenerated endothelium • endothelium-derived hyperpolarizing factor • serotonin • bradykinin
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