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The Protective Effects of Monophosphoryl Lipid A on the Ischemic Myocardium and Endothelium in Rats

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Abstract

Previous investigations have shown that a single dose of low-density lipoprotein (LDL) injection causes a marked decrease in endothelium-dependent relaxation, and that endothelial dysfunction aggravates myocardial injury due to ischemia-reperfusion in atherosclerotic animals. Monophosphoryl lipid A-induced delayed preconditioning preserves the ischemic myocardium and endothelial cells. The objective of the present study was to examine the effect of monophosphoryl lipid A on endothelial function and ischemia-reperfusion-induced myocardial injury in the rats treated with LDL. A single injection of native LDL (4 mg/kg, i.v.) caused a significant decrease in vasodilator responses to acetylcholine and an increase in the serum level of asymmetric dimethylarginine, the endogenous nitric oxide synthase inhibitor. Pretreatment with monophosphoryl lipid A (300 or 450 μg/kg, i.p.) significantly improved endothelium-dependent relaxation and decreased concentrations of asymmetric dimethylarginine, and the effects of monophosphoryl lipid A were attenuated by L-nitro-arginine-methylester, but not by aminoguanidine. LDL treatment only aggravated the decreased coronary flows but did not affect cardiac dysfunction due to ischemia-reperfusion in the rats treated with LDL. Pretreatment with monophosphoryl lipid A significantly improved cardiac dysfunction by ischemia-reperfusion in the rats treated with or without LDL, an effect that was abolished by aminoguanidine. The present study suggests that: (1) a single injection of native LDL causes a decrease in endothelium-dependent relaxation, and aggravates the decrease of coronary flow due to ischemia-reperfusion, (2) pretreatment with monophosphoryl lipid A protects the myocardium against ischemia-reperfusion in the rats treated with or without native LDL, and (3) the protective effect of monophosphoryl lipid A on endothelial cells is related to reduction of asymmetric dimethylarginine level.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410078, P.R. China

    Hui-Qing Zhu, Jun-Lin Jiang, Rong Lu, Xiao-Hong Zhang, Han-Wu Deng & Yuan-Jian Li

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  1. Hui-Qing Zhu
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  2. Jun-Lin Jiang
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Zhu, HQ., Jiang, JL., Lu, R. et al. The Protective Effects of Monophosphoryl Lipid A on the Ischemic Myocardium and Endothelium in Rats. Cardiovasc Drugs Ther 17, 311–318 (2003). https://doi.org/10.1023/A:1027335321530

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