Bupivacaine-induced contraction is attenuated by endothelial nitric oxide release modulated by activation of both stimulatory and inhibitory phosphorylation (Ser1177 and Thr495) of endothelial nitric oxide synthase

Linolenic Acid Attenuates the Vasodilation Induced by Acetylcholine in Isolated Rat Aortae

“…In agreement with previous reports using aminoamide local anesthetics, the vasodilation induced by a toxic concentration (3 × 10 −4 M) of bupivacaine is mediated by NO (Figure 7B). 11-13,18,35 In addition, a lipid emulsion containing linolenic acid reverses vasodilation induced by a toxic concentration of levobupivacaine in endothelium-intact aortae and reduces levobupivacaine-induced eNOS phosphorylation in human umbilical vein endothelial cells and rat aortic endothelium. 14,15 Taken together, the evidence suggests that linolenic acid-induced inhibition of vasodilation caused by NO observed in the current study appears to partially contribute to lipid emulsion-mediated inhibition of severe vasodilation (vascular collapse) caused by NO release induced by toxic concentrations of local anesthetics.…”

“…Consistent with a previous study, a toxic concentration of bupivacaine (3 Â 10 À4 M) induced eNOS phosphorylation ( Figure 8B). 18 However, calcium-dependent vascular smooth muscle contraction activates calciumdependent phosphodiesterase to reduce cGMP levels. 29 Thus, although bupivacaine increased eNOS phosphorylation ( Figure 8B), the bupivacaine-induced decrease in the cGMP level observed in the endothelium-intact aortic strip ( Figure 9B) seems to be due to the antagonizing effect of calciumdependent bupivacaine-induced smooth muscle contraction ( Figure 7A) on the endothelial NO-induced cGMP production induced by bupivacaine in the isolated endothelium-intact aortic strip.…”

“…14,15 Taken together, the evidence suggests that linolenic acidinduced inhibition of vasodilation caused by NO observed in the current study appears to partially contribute to lipid emulsion-mediated inhibition of severe vasodilation (vascular collapse) caused by NO release induced by toxic concentrations of local anesthetics. [11][12][13][14][15]18 In addition, as linolenic acid increased dexmedetomidine-induced contraction in endothelium-intact aortae, a patient concurrently taking Intralipid and dexmedetomidine for parenteral nutrition and sedation, respectively, in the intensive care unit may show slightly increased blood pressure compared with a patient taking only dexmedetomidine. However, this study has some limitations.…”

“…In addition, as bupivacaine-induced contraction is attenuated by endothelial NO release, the effect of linolenic acid on the bupivacaine-induced contraction in endothelium-intact and endothelium-denuded aortae was investigated. 18 The endothelium-intact rat aortae were pretreated with linolenic acid (5 × 10 −5 M) or l -NAME (10 −4 M) alone for 20 minutes or l -NAME (10 −4 M) for 20 minutes followed by linolenic acid (5 × 10 −5 M) for 20 minutes. In addition, the endothelium-denuded aortae were pretreated with linolenic acid (5 × 10 −5 M) for 20 minutes.…”

“…Isolated rat aortae for isometric tension measurement were prepared as described previously. 18,19 Carbon dioxide (100%) was used to euthanize male Sprague-Dawley (body weight: 250-300 g). The descending thoracic part of the aorta was dissected and removed from the thorax.…”