Endothelin induces vasoconstriction in the bone vasculature in vitro: An effect mediated by a single receptor population

The aim of this study was to define the types of endothelin receptors present in the canine tibial vasculature. Endothelin receptor agonists and antagonists were used in two different models: isolated nutrient tibial arteries in organ bath and in vitro-perfused canine tibial bones. In isolated nutrient tibial arteries, endothelin-1 caused concentration-dependent contractions of rings with and without endothelium. BQ-123, a selective endothelin-A antagonist, induced a significant rightward shift of endothelin-1 concentration-response curves. No contractions were observed with sarafotoxin S6c, a selective endothelin-B agonist. The responses of endothelin-1 were not affected by the presence of N^G-monomethyl-L-arginine acetate plus indomethacin or by removal of the endothelium. In perfused tibial bones, endothelin-1 was more potent than endothelin-3 in causing concentration-dependent contractions. Neither endothelin-1, endothelin-3, nor sarafotoxin S6c caused relaxations. Neither the inhibition of nitric oxide nor the inhibition of prostaglandins significantly altered contractions to endothelin-1. These concordant data indicate that endothelin is a vasoconstrictor in the bone vasculature, an effect that appears to be mediated only through endothelin-A receptors.