Comparison of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation‐mediated vascular contraction

Abstract

Isoflurane induces greater effects on vasodilation and decreasing blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in regulating vascular smooth muscle contraction. The aim of the present study was to compare the effects of isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular constriction, by assessing the degree of sodium orthovanadate (Na(3)VO(4), tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle. Na(3)VO(4)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were measured in the presence of genistein, a tyrosine kinase inhibitor, and different concentrations of isoflurane and sevoflurane, using isometric force measurement and Western blot, respectively. Na(3)VO(4) (10(-4) M) induced sustained contraction and tyrosine phosphorylation of substrates that were both markedly attenuated in the presence of genistein (5 x 10(-5) M). Isoflurane and sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na(3)VO(4)-induced contraction (P < 0.05-0.005, n = 8), with a greater degree of inhibition by isoflurane than sevoflurane at 2 MAC (P < 0.01) and 3 MAC (P < 0.05). Both anesthetics also attenuated the total band density of the Na(3)VO(4)-induced, tyrosine-phosphorylated substrates in a concentration-dependent manner (P < 0.05-0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1 and 2 MAC (P < 0.05), respectively. The results of the present study demonstrate that isoflurane exhibits a greater degree of inhibition on the Na(3)VO(4)-stimulated contraction and protein tyrosine phosphorylation of rat aortic smooth muscle compared with sevoflurane. These findings suggest that isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of vascular smooth muscle to a greater degree than sevoflurane.