Endothelin-induced contraction and relaxation of rat isolated basilar artery: effect of BQ-123.
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.
Feger
G I
GI
Department of Physiology, University of Munich, Germany.
Schilling
L
L
Ehrenreich
H
H
Wahl
M
M
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)