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: Hui-Qing Zhu, Jun-Lin Jiang, Rong Lu, Xiao-Hong Zhang, Han-Wu Deng, Yuan-Jian Li
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 17 Issue 4 Pg. 311-8 (Jul 2003) ISSN: 0920-3206 [Print] United States
• PMID: 14618092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, LDL
• Lipid A
• N,N-dimethylarginine
• Arginine
• Creatine Kinase
• monophosphoryl lipid A

Topics

• Animals
• Arginine (analogs & derivatives, blood)
• Cholesterol, LDL (pharmacology)
• Creatine Kinase (blood)
• Endothelium, Vascular (drug effects, physiopathology)
• Heart (drug effects)
• Lipid A (analogs & derivatives, metabolism, pharmacology)
• Male
• Myocardial Reperfusion Injury (metabolism, physiopathology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Vasodilation (drug effects)