Endothelin-1-induced responses in isolated mouse vessels: The expression and function of receptor types

Mice have been increasingly used as models for investigating cardiovascular diseases. However, the responsiveness of mouse vasculature to endothelin (ET)-1 has not been clearly established. The goal of this study was to determine the role of ET receptors (ET_A and ET_B) in mouse vessels using isometric force measurements. Results showed that in the abdominal aorta ET-1 induced a concentration-dependent contraction (EC₅₀: 1.4 nM) with maximum reaching 89.5 ± 4.9% (10 nM) of that induced by 60 mM K ⁺ [with nitric oxide synthase (NOS) inhibitor N^ω- nitro-L-arginine methyl ester (L-NAME)]. However, in the thoracic aorta or the carotid artery, ET-1 was poorly effective. RT-PCR revealed that in the endothelium-denuded abdominal aorta, the PCR product for ET_B receptors was very low compared with ET_A. Similarly in tissues treated with L-NAME, the ET_B receptor-specific agonist sarafotoxin 6c (S6c; 100 nM) induced only a minimal contraction (A antagonist BQ-123 (1 μM) completely inhibited the maximum ET-1 (10 nM) contractile response. Furthermore, we found that in the abdominal aorta that had not been treated with L-NAME, ET-1-induced contraction significantly decreased. However, in such specimens, S6c was unable to induce any relaxation on phenylephrine-induced contraction. These results indicate that the role of ET receptors differs considerably among mouse vessels. In the abdominal aorta, ET_A receptor mediates a potent vasoconstrictor response, whereas ET_B has, if any, only a minimal functional presence. Also, our data suggest that ET-1 might involve a NOS-dependent vasodilation in the abdominal aorta, which remains to be further defined.