Sevoflurane Inhibits Guanosine 5′-[γ-thio]triphosphate-stimulated, Rho/Rho-kinase-mediated Contraction of Isolated Rat Aortic Smooth Muscle

Background: The Rho/Rho-kinase signaling pathway plays an important role in mediating Ca2+ sensitization of vascular smooth muscle. The effect of anesthetics on Rho/Rho-kinase-mediated vasoconstriction has not been determined to date. This study is designed to examine the possible inhibitory effects of sevoflurane on the Rho/Rho-kinase pathway by measuring guanosine 5'-gamma]-thio]triphosphate (GTPgamma]S)-stimulated contraction and translocation of RhoA (one of the three Rho subtypes) and Rock-2 (one of the two Rho-kinase subtypes) from the cytosol to the membrane in rat aortic smooth muscle.

Methods: GTPgamma]S-induced contraction of rat aortic endothelium-denuded rings was measured using an isometric force transducer, and GTPgamma]S-stimulated membrane translocation of RhoA and Rock-2 in smooth muscle cells was detected with Western blotting in the presence and absence of sevoflurane.

Results: GTPgamma]S (10-4 m) induced a sustained contraction, which was significantly inhibited by the Rho-kinase inhibitor, Y27632 (3 x 10-6 m). Before treatment with GTPgamma]S, RhoA and Rock-2 were detected primarily in the cytosolic fraction. GTPgamma]S (10-4 m) stimulated the translocation of RhoA and Rock-2 from the cytosol to the membrane, which was sustained for more than 60 min. Sevoflurane (1.7, 3.4, and 5.1%) concentration dependently inhibited the GTPgamma]S-induced constriction of rat aortic smooth muscle with a reduction of constriction of 52-75% (P < 0.01, n = 8), and attenuated the translocation of RhoA and Rock-2 by 31-66% and 34-78%, respectively (P < 0.05-0.01, respectively; n = 4).