ABSTRACT
Transmembrane potential, isometric tension and levels of cyclic-Guanosine Mono phosphate and cyclic-Adenosine Monophosphate (cyclic G M P and cyclic A M P ) were measured simultaneously in each strip with regenerated endothelium and compared with those of the corresponding control coronary artery. Under basal conditions, in coronary arteries with regenerated endothelium, a depolarization of vascular smooth muscle cells was associated with a decreased level of cyclic G M P without alteration in that of cyclic A M P . Exogenous nitric oxide (NO) was added in order to compensate for the reduced level of cyclic G M P . The resulting repolarization of the injured coronary arteries demonstrated the involvement of the N O pathway in the control of resting membrane potential. This effect was cyclic GMP-dependent, as it was blocked by an inhibitor of soluble guanylate cyclase, oxadiazoloquinoxalin (ODQ). When contracted with prostaglandin F2a , arteries with normal or regenerated endothelium depolarized whatever the conditions studied (control, inhibition of cycloxygenase with or without that of nitric oxide synthase). In the presence of regenerated endothelium, spikes and phasic contraction were observed. In all blood vessels, both in the presence or the absence of indomethacin, bradykinin evoked nearly maximal relaxations suggesting no involvement of prostacyclin in the response. Additional blockade of nitric oxide syn thase by N^-nitro-L-arginine, reduced the relaxation, demonstrating a small contribu tion of N O . In both coronary arteries, the relaxation induced by bradykinin was mediated essentially by E D H F . The membrane potential reached during exposure to bradykinin was always less negative in the presence of regenerated endothelium, suggesting that the N O pathway participated to the hyperpolarization in repolarizing the blood vessel. Thus, the unaltered relaxation to bradykinin despite the reduced production of N O , suggests that the endothelium-dependent hyperpolarization is sufficient to maintain a normal relaxation in coronary arteries with regenerated endothelium.
