ENDOTHELIN-INDUCED CONTRACTION AND RELAXATION OF RAT ISOLATED BASILARARTERY - EFFECT OF BQ-123

In ring segments from rat basilar artery (BA) the endothelin (ET) pept ides ET-1, ET-2, and ET-3 induced concentration-relate d contractions. The order of potency was ET-1 = ET-2 > ET-3, while no differences occ urred in the maximum contraction. The selective ET, receptor antagonis t, BQ-123 (10(-10)-10(-4) M) alone elicited a small contraction only a t 10(-4) M. In the presence of BQ-123 (10(-7)-10(-5) M), the concentra tion-response curve for ET-1 was shifted to the right without any decr ease in maximum contraction, indicating competitive inhibition of ET-1 binding to the ET(A) receptor by BQ-123. The pA(2) value calculated f or BQ-123 was 6.935; the slope of the regression curve was 0.734. In c ontrast to ET-1, the contractile action of ET-3 was abolished by 10(-5 ) M BQ-123. In segments precontracted with 10(-6) M serotonin, ET-3, b ut not ET-1, induced relaxation at low concentrations (10(-11)-10(-9) M), with maximum relaxation amounting to 17.8 +/- 14.7% of precontract ion (mean +/- SD; n = 16). The relaxant action of ET-3 was abolished i n vessels incubated with NG-nitro-L-arginine (10(-5) M), an inhibitor of nitric oxide synthase. These results indicate that the ET-induced c ontraction of the isolated rat BA involves activation of the ET(A) rec eptor. The ET-3-induced relaxation of precontracted rat BA is apparent ly mediated by release of nitric oxide from the endothelium.