C. Thollon et al., Alteration of endothelium-dependent hyperpolarizations in porcine coronaryarteries with regenerated endothelium, CIRCUL RES, 84(4), 1999, pp. 371-377
The present study was designed to test the ability of regenerated endotheli
um to evoke endothelium-dependent hyperpolarizations. Hyperpolarizations in
duced by serotonin and bradykinin were compared in isolated porcine coronar
y arteries with native or regenerated endothelium. 4 weeks after balloon en
dothelial denudation. The experiments were performed in the presence of inh
ibitors of nitric oxide synthase (N-omega-nitro-L-arginine) and cyclooxygen
ase (indomethacin). The transmembrane potential was measured using conventi
onal glass microelectrodes. Smooth muscle cells from coronary arteries with
regenerated endothelium were depolarized in comparison with control corona
ry arteries from the same hearts. Spontaneous membrane potential oscillatio
ns of small amplitude or spikes were observed in some of these arteries but
never in arteries with native endothelium. In coronary arteries from contr
ol pigs, both serotonin and bradykinin induced concentration-dependent hype
rpolarizations. In the presence of ketanserin, 10 mu mol/L serotonin induce
d a transient hyperpolarization in control coronary arteries. Four weeks af
ter balloon denudation, the response to serotonin was normal in arteries wi
th native endothelium, but the hyperpolarization was significantly lower in
coronary arteries with regenerated endothelium. In control arteries, the e
ndothelium-dependent hyperpolarization obtained with bradykinin (30 nmol/L)
was reproducible. Four weeks after balloon denudation, comparable hyperpol
arizations were obtained in coronary arteries with native endothelium. By c
ontrast, in arteries with regenerated endothelium, the hyperpolarization to
bradykinin became voltage-dependent. In the most depolarized cells, the hy
perpolarization to bradykinin was augmented. The changes in resting membran
e potential and the alteration in endothelium-dependent hyperpolarizations
observed in the coronary arteries with regenerated endothelium may contribu
te to the reduced response to serotonin and the unchanged relaxation to bra
dykinin described previously.