Abstract
An in vitro model of endothelial cell injury was used to investigate the role of endothelins and related peptides in endothelial repair. Endothelin-3 (10-100 nM) enhanced wound repair over an 18 h period by promoting proliferation, an effect not inhibited by the specific ET A receptor antagonist BQ-123 (100 nM) or the mixed ET A/ET B antagonist PD142893 (10 μM). Like endothelin-3, the ET B selective agonists [Ala 1,3,11,15]endothelin-1 and sarafotoxin S6c were able to enhance wound repair over the same dose range. Neither endothelin-l nor endothelin-2, however, had any effect on endothelial cell wound healing. Inhibition of cyclo-oxygenase or neutralisation of basic fibroblast growth factor did not inhibit this endothelin-3-mediated event. These results suggest that endothelin-3 might have a direct role in endothelial cell proliferation as a response to injury which is not mediated by either of the currently defined ET A and ET B receptors.
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