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Endothelin‐1-Induced Contraction and Relaxation of Isolated Rat Basilar Artery: Effect of the Endothelium

Summary: In rat basilar artery ring segments precontracted with prostaglandin (PG)F2a, endothelin (ET)-3 induced a concentration-related relaxation at doses of 3 x 10 -10 to 1 x 10 -8 M, whereas contraction occurred at higher concentrations. In contrast, relaxation by ET-1 was observed only in the presence of an ETA receptor antagonist. The ET-induced relaxation could be blocked by an ETB receptor antagonist and by a nitric oxide (NO) synthase inhibitor, suggesting activation of an ETB receptor. This receptor, which may be located on the endothelium, is apparently coupled to release of NO. Under resting tension, ET-1 and ET-3 induced concentration-related contractions, which were enhanced after NO synthase inhibition or after de-endothelialization. These results suggest simultaneous induction of contraction and relaxation by the ETs. With ET-1, this occurs in the same concentration range, with the relaxing effect being masked by the contraction.