抄録
Endothelin-1 (ET-1), a potent vasoconstrictor peptide, induces a long-lasting contraction mediated by G protein-coupled endothelinA (ETA) receptor in aortic smooth muscle. In isolated rat aorta without endothelium, the ET-1 (100 nM)-induced contraction was very slowly relaxed by perfusion of the aorta with physiological salt solution without ET-1, and it was incompletely inhibited by application of the ETA receptor antagonist BQ-123 (10 μM) during the plateau tension. These relaxations were enhanced and completely performed by addition of the Rho-associated kinase inhibitor Y-27632 (10 μM) to the perfusion solution or by the combined application of BQ-123 (10 μM) and Y-27632 (10 μM). The enhanced relaxation rates were much higher than the relaxation rate for the application of Y-27632 (10 μM) alone which completely inhibited the ET-1 (100 nM)-induced contraction. In Ca2+-free solution or in the presence of the myosin light chain kinase inhibitor wortmannin (10 μM), ET-1 (100 nM) evoked a contraction which was completely inhibited by Y-27632. This result shows that the contraction in the Ca2+-free solution or insensitive to wortmannin is induced through myosin light chain phosphorylation by Rho-associated kinase. The contraction through the activation of Rho-associated kinase was fairly resistant to BQ-123. The present results would suggest that the small GTPase Rho and its effector, Rho-kinase, pathway is involved in the binding affinity of ET-1 to the ETA receptor in rat aorta. [J Physiol Sci. 2008;58 Suppl:S69]
