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Delayed endothelial protective effects of monophosphoryl lipid A after myocardial ischemia and reperfusion in rats.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 1999 May; Vol. 31 (5), pp. 1117-23. - Publication Year :
- 1999
-
Abstract
- Monophosphoryl lipid A (MLA) induces delayed (24 h) myocardial protection in various animal models of ischemia/reperfusion injury, and thus mimics the second window of preconditioning against cardiac injury. However, the potential endothelial protective effects of this drug have not been evaluated. The present study was designed to assess whether MLA exerts delayed protective effects against reperfusion-induced coronary endothelial dysfunction in rats, as well as the protective role of iNOS in this protection. Wistar rats received a single i.v. injection of MLA (450 microg/kg) or solvent. Twenty-four hours later, they were anesthetized and subjected to 20 min ischemia with 60 min reperfusion, in the absence or the presence of the iNOS inhibitor aminoguanidine (300 mg/kg i.p.). At the end of reperfusion, 1.5-2 mm coronary segments (average diameter 250 microm) were removed distal to the site of occlusion and mounted in wire myographs. Endothelium-dependent relaxations to acetylcholine were determined in arteries pre-contracted by serotonin. Ischemia/reperfusion induced a marked decrease in the coronary responses to acetylcholine (maximal relaxations: sham 64+/-8%, n=8; ischemia/reperfusion: 41+/-9%, n=8 P<0.05). This impaired response was partially restored by MLA (55+/-4%, n=10 P<0.05 vs ischemia/reperfusion). The effect of MLA was not affected by aminoguanidine (57+/-5%, n=6). Thus, in addition to protecting myocytes, MLA induces a delayed protection against coronary endothelial dysfunction. However, in contrast to its effects on myocytes, the endothelial protective effects do not appear to involve iNOS.<br /> (Copyright 1999 Academic Press.)
- Subjects :
- Acetylcholine pharmacology
Animals
Cytoprotection
Lipid A pharmacology
Logistic Models
Male
Molsidomine analogs & derivatives
Molsidomine pharmacology
Nitric Oxide Synthase metabolism
Nitric Oxide Synthase Type II
Rats
Rats, Wistar
Serotonin pharmacology
Time Factors
Vasodilator Agents pharmacology
Adjuvants, Immunologic pharmacology
Endothelium, Vascular drug effects
Lipid A analogs & derivatives
Myocardial Reperfusion Injury drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2828
- Volume :
- 31
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 10336849
- Full Text :
- https://doi.org/10.1006/jmcc.1999.0943