Sevoflurane and isoflurane inhibit KCl-induced, Rho kinase-mediated, and PI3K-participated vasoconstriction in aged diabetic rat aortas

BACKGROUND: The mechanism of volatile anesthetics on vascular smooth muscle (VSM) contraction in the setting of diabetes mellitus (DM) remains unclear. The current study was designed to determine the effects of sevoflurane (SEVO) and isoflurane (ISO) on phosphoinositide 3-kinase (PI3K) and Rho kinase (ROCK) mediated KCl-induced vasoconstriction in aged type 2 diabetic rats. METHODS: KCl-induced (60 mM) contractions were examined in endothelium-denuded aortic rings from aged T2DM Otsuka Long-Evans Tokushima Fatty (OLETF) rats (65–70 weeks old), control age-matched nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and young Wistar rats (6–8 weeks old). The effects of SEVO or ISO (1–3 minimum alveolar concentration, MAC) on KCl-induced vasoconstriction, as well as those of LY294002 (PI3K inhibitor) and Y27632 (ROCK inhibitor) were measured in aortic rings from the three groups using an isometric force transducer. RESULTS: KCl induced rapid and continuous contraction of aortic smooth muscle in the three groups, and the contraction was more obvious in OLETF rats. SEVO and ISO inhibited KCl-induced vasoconstriction in a concentration-dependent manner and were suppressed by LY294002 (10 µM) and Y27632 (1 µM). SEVO had a stronger inhibitory effect on the aortas of young Wistar rats than ISO, especially at 2 MAC and 3 MAC (P < 0.05). In aged rats, the inhibitory effect of ISO was stronger than that of SEVO, especially OLETF rats. There was no significant difference in the effects of different concentrations of ISO on arterial contraction among the three groups (P > 0.05). The effects of 1 MAC SEVO on Wistar rats and 3 MAC SEVO on OLETF rats, however, were noticeably and significantly different (P < 0.05). Compared with the control condition, LY294002 and Y27632 had the most noticeable effect on the KCl-induced contraction of aortic rings in OLETF rats (P < 0.01). CONCLUSION: SEVO (3 MAC), ISO (1, 2, 3 MAC), LY294002 and Y27632 have more significant inhibitory effect on the contraction of vascular smooth muscle in aged T2MD rats. The mechanism of SEVO and ISO in vascular tension in T2DM is partly due to changes in PI3K and/or Rho kinase activity.