Endothelin receptors mediating contraction in goat cerebral arteries

1 The aim of the present study was to identify the subtype of receptor mediating contraction to endothelin‐1 and sarafotoxin S6b in goat isolated middle cerebral arteries. 2 Endothelin‐1, endothelin‐2 and endothelin‐3 contracted cerebral arteries in a concentration‐dependent manner. Although the three peptides were full agonists, the order of potency was endothelin‐1 = endothelin‐2 > endothelin‐3, with a relative potency of endothelin‐1 and endothelin‐2 versus endothelin‐3 of ∼280. Sarafotoxin S6b induced concentration‐dependent contractions with lower potency than endothelin‐1/endothelin‐2, higher potency than endothelin‐3 and a higher maximum response than the three endothelins. 3 The selective ET A ‐receptor antagonist, BQ‐123, did not induce changes in either the resting tension or in the active tone developed by depolarization. In contrast, BQ‐123 produced concentration‐dependent relaxations of endothelin‐1‐precontracted cerebral arteries, and to a greater extent of sarafotoxin S6b‐precontracted arteries. 4 Concentration‐response curves to endothelin‐1 and sarafotoxin S6b were competitively antagonized by BQ‐123 (pA 2 of 7.43 ± 0.12 and 8.41 ± 0.09, respectively). In contrast, BQ‐123 had no effect on 5‐hydroxytryptamine‐elicited contractions even at 10 −6 M. 5 It is concluded that both the order of potency of endothelin isopeptides and the antagonism of BQ‐123 point to the existence of ET A receptors mediating vasoconstriction to endothelin‐1 and sarafotoxin S6b in the goat middle cerebral artery. The different antagonistic potency of BQ‐123 against endothelin‐1 and sarafotoxin S6b suggests the existence of subtypes of ET A receptors.