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 bone s. In isolated nutrient tibial arteries, endothelin-1 caused concentra tion-dependent contractions of rings with and without endothelium. BQ- 123, a selective endothelin-A antagonist, induced a significant rightw ard shift of endothelin-1 concentration-response curves. No contractio ns were observed with sarafotoxin S6c, a selective endothelin-B agonis t. The responses of endothelin-1 were not affected by the presence of N-G-monomethyl-L-arginine acetate plus indomethacin or by removal of t he endothelium. In perfused tibial bones, endothelin-1 was more potent than endothelin-3 in causing concentration-dependent contractions. Ne ither endothelin-1, endothelin-3, nor sarafotoxin S6c caused relaxatio ns. Neither the inhibition of nitric oxide nor the inhibition of prost aglandins significantly altered contractions to endothelin-1. These co ncordant data indicate that endothelin is a vasoconstrictor in the bon e vasculature, an effect that appears to be mediated only through endo thelin-A receptors.