title: The protective effects of monophosphoryl lipid A on the ischemic myocardium and endothelium in rats.
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 microg/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.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, P.R. China.
authors: Hui-Qing
authors: HQ
authors: Zhu
authors: Jun-Lin
authors: JL
authors: Jiang
authors: Rong
authors: R
authors: Lu
authors: Xiao-Hong
authors: XH
authors: Zhang
authors: Han-Wu
authors: HW
authors: Deng
authors: Yuan-Jian
authors: YJ
authors: Li
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D008078:Cholesterol, LDL / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008078:Cholesterol, LDL; D008050:Lipid A; C018524:N,N-dimethylarginine; D001120:Arginine; D003402:Creatine Kinase; C048436:monophosphoryl lipid A