Endothelium-dependent relaxation induced by etomidate in the aortas of insulin-resistant rats

Few reports have mentioned the effect of etomidate on the aortas of insulin-resistant (IR) rats. In this study, we investigated the effect of etomidate on isolated IR aortas of rats, and explored its underlying mechanism.

The IR rat model was established through feeding with a high-fructose diet. The systolic blood pressure (SBP) was measured by the tail-cuff method before grouping and at the end of the 8-week feeding; blood samples were also obtained for analysis. Thoracic aorta rings of IR rats were isolated and suspended in a tissue bath. The tensile force was recorded isometrically. The effect of etomidate on provoked contraction of the rings was assessed with or without a potassium channel blocker or NO synthase inhibitor.

Etomidate-induced relaxation in IR rings was greater than normal control (NC) rings (all p < 0.001 with etomidate log M of -4 to -6). NG-nitro-L-arginine methyl ester (L-NAME, an NO synthase inhibitors) inhibited etomidate-induced relaxation in NC rings, but had no effect on the IR rings (all p < 0.001 with etomidate log M of -4 to -6). Pre-incubation with glibenclamide (Gli, a potassium channel blocker) significantly inhibited etomidate-induced relaxation in NC and IR rings (all p < 0.001 with etomidate log M of -4 to -6), and had no inhibited effect on endothelial denuded aortic rings.

Insulin resistance increased etomidate-induced relaxation in rat aortas. Etomidate causes vasodilation in IR rat aortas via both endothelium-dependent and independent ways; impaired NO-mediated relaxation was disrupted and ATP-sensitive potassium (K_ATP) channel-mediated relaxation may be involved in the endothelium-dependent relaxation of etomidate in IR rats.