Endothelin-Induced Contraction and Relaxation of Rat Isolated Basilar Artery: Effect of BQ-123

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Abstract
In ring segments from rat basilar artery (BA) the endothelin (ET) peptides ET-1, ET-2, and ET-3 induced concentration-related contractions. The order of potency was ET-1 = ET-2 > ET-3, while no differences occurred in the maximum contraction. The selective ETA receptor antagonist, BQ-123 (10−10-10−4 M) alone elicited a small contraction only at 10−4 M. In the presence of BQ-123 (10−7-10−5 M), the concentration-response curve for ET-1 was shifted to the right without any decrease in maximum contraction, indicating competitive inhibition of ET-1 binding to the ETA receptor by BQ-123. The pA2 value calculated for BQ-123 was 6.935; the slope of the regression curve was 0.734. In contrast 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, but not ET-1, induced relaxation at low concentrations (10−11-10−8 M), with maximum relaxation amounting to 17.8 ± 14.7% of precontraction (mean ± SD; n = 16). The relaxant action of ET-3 was abolished in vessels incubated with NG-nitro-l-arginine (10−5 M), an inhibitor of nitric oxide synthase. These results indicate that the ET-induced contraction of the isolated rat BA involves activation of the ETA receptor. The ET-3-induced relaxation of precontracted rat BA is apparently mediated by release of nitric oxide from the endothelium.

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