Alteration of endothelium-dependent hyperpolarizations in porcine coronaryarteries with regenerated endothelium

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.