Ropivacaine-induced contraction is attenuated by both endothelial nitric oxide and voltage-dependent potassium channels in isolated rat aortae.

This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS) inhibitor N (ω) -nitro-L-arginine methyl ester (L-NAME), the neuronal NOS inhibitor N (ω) -propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC) inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP), the calcium-activated potassium channel inhibitor tetraethylammonium (TEA), the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, N (ω) -propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

Effect of two lipid emulsions on reversing high-dose levobupivacaine-induced reduced vasoconstriction in the rat aortas.

The goals of this study were to determine which lipid emulsion (Intralipid(®) and Lipofundin MCT/LCT(®)) is more effective in reversing high-dose levobupivacaine-induced reduced vasoconstriction in isolated rat aortas and to examine the associated cellular mechanisms with a particular focus on the endothelium. Two lipid emulsion concentration-response curves were generated using high-dose levobupivacaine-induced reduced vasoconstriction and vasodilation of isolated aortas pretreated with or without 60 mM KCl. Endothelial nitric oxide synthase (eNOS) and caveolin-1 phosphorylation were measured in rat aortic tissue treated with levobupivacaine in the presence or absence of lipid emulsion. Dichlorofluorescein oxidation, a measure of reactive oxygen species production, was measured in lipid emulsion-treated human umbilical vein endothelial cells. In levobupivacaine (0.3 mM)-induced reduced vasoconstriction of isolated aorta, the magnitude of the Intralipid(®)- and Lipofundin MCT/LCT(®)-mediated reversal was not significantly different. Lipid emulsion reversal of levobupivacaine-induced reduced vasoconstriction was greater in endothelium-intact aortas than in endothelium-denuded aortas. The two lipid emulsions similarly inhibited levobupivacaine-induced eNOS phosphorylation in aortic tissue. Pretreatment with both lipid emulsions increased dichlorofluorescein oxidation. Both Intralipid(®) and Lipofundin MCT/LCT(®) are equally effective for vascular tone recovery from high-dose levobupivacaine-induced reduced vasoconstriction. This reversal is mediated partially by decreasing nitric oxide bioavailability.