Endothelin and Ca ++ agonist bay K 8644: Different vasoconstrictive properties

The mechanism of vasoconstriction induced by endothelin was investigated in rat isolated aorta in comparison with the Ca ++ agonist, Bay K 8644. Endothelin (EC 50=4 nM) induced a slow and sustained contraction in control medium whereas the one elicited by Bay K 8644 (EC 50=14 nM) necessitating a partly K + depolarized medium was fast with superimposed rhythmic contraction. By opposition with Bay K 8644, endothelin contraction was not inhibited by the calcium antagonists (1 μM), nifedipine, diltiazem and D 600, and substantially persisted in Ca ++ free medium or after depletion of intracellular Ca ++ by phenylephrine (1 μM). These data show that endothelin does not act as an activator of potential dependent Ca ++ channels but probably through specific receptor(s) as suggested by its mode of vasoconstriction.