The Influence Of Lipid Emulsion On The Function Of Isolated Vascular And Endothelial Cells

Objective: Intravenous Lipid emulsion?LE?has been widely used for parenteral nutrition in clinic.In recent years,more and more studies found non-nutritional role of LE for example as the antidote for some local anesthetics.In addition,some studies found that intravenous LE could increase blood pressure in healthy people,but the mechanism is unclear.Our previous studies also showed that LE could attenuate the endotheliumdependent relaxation response to acetylcholine in aortic rings.To further clarify the mechanism of LE reversing vasodilatation,we studied the effect of LE on the vascular function in aortic ring and the intracellular calcium in endothelial cell.Methods:1 The isolated rat aortic rings were prepared and suspended in an organ bath.We observe the effect of LE on vasoconstriction induced by phenylephrine?Phe?and the vasodilatation induced by acetylcholine?Ach?.2 The Human aortic endothelial cells were cultured.Intracellular calcium of endothelial cell was recorded by calcium imaging system.Results:1 The effect of 0.4% LE on the vasoconstriction and vasodilatation in the isolated rat aortic rings.?1?0.4% LE preincubation 5 minutes failed to affect the vasoconstriction response induced by Phe?P>0.05?.?2?0.4%LE pretreatment 5 minutes significant inhibited the vasodilation induced by Ach and shifted the dose-response curve to right direction?P< 0.05?.2 The influence of LE on the [Ca²⁺]i in human aortic endothelial cells.?1?0.4% LE could inhibit [Ca²⁺]i increase induced by Ach?3?M??P<0.05?.?2?Pretreatment with 0.4%LE for 5 minutes significantly inhibited the [Ca²⁺]i increase induced by ATP?10?M?in endothelial cells.?3?Different concentrations of Lipid emulsion?0.2%,0.4%,0.8%,2.5% LE?had different effect of.Only 0.4% and 0.8% LE had most obvious effect on the [Ca²⁺]i in endothelial cell?P<0.05?.0.4% LE incubated for different time?2min,5min,and 15min?could inhibit the ATP mediated [Ca²⁺]i increased in endothelial cells.?4?When chelated the extracellular calcium by 0.1mM EGTA,0.4% LE still can inhibit the ATP mediated [Ca²⁺]i increased in endothelial cells?P<0.001?.?5?Preincubation of 0.4%LE 5min significantly inhibited [Ca²⁺]i increased induced by CPA?P<0.001?.?6?Bupivacaine?300?M?significantly increased the [Ca²⁺]i in endothelial cell.?7?The release of NO was significantly inhibited by pretreatment with 0.4%LE for1 hour?P<0.05?.Conclusion:1 In the isolated rat aortic rings LE could reverse the Ach-induced vasodilatation.2 LE inhibited the ATP induced intracellular calcium increase by inhibition the calcium release from endoplasmic reticulum,which ultimately reduced the production of NO and suppressed vascular relaxation.