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

1 Department of Physiology and Cell Biology and 2 Davis Heart and Lung Research Institute, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210 Submitted 9 December 2003 ; accepted in final form 7 April 2004 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 (EC 50 : 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 -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 (