Sulfhydryl compounds, captopril, and MPG inhibit complement-mediated myocardial injury.
Factors including complement activation, neutrophil infiltration, and oxygen-derived free radicals have been implicated in the pathogenesis of myocardial tissue injury during ischemia and reperfusion. Certain sulfhydryl-containing compounds have been shown to inhibit complement activation. The sulfhydryl compounds captopril and N-(2-mercaptopropionyl)-glycine (MPG) are antioxidant compounds that previously have been shown to protect the myocardium from ischemia and reperfusion-induced damage. In this study, captopril (an angiotensin-converting-enzyme inhibitor; ACEI) and MPG, and the non-sulfhydryl compound enalaprilat (also an ACEI) were tested for their ability to protect the isolated perfused rabbit heart against complement-induced injury. Both captopril and MPG protected hearts against complement-mediated increases in left ventricular end-diastolic pressure and increases in coronary arterial perfusion pressure in a concentration-dependent manner, whereas enalaprilat was not protective. The ability of these compounds to inhibit complement activation also was tested using an in vitro complement-mediated red blood cell hemolysis assay. These findings offer additional insight as to the mechanism whereby captopril, MPG, and possibly other sulfhydryl compounds, may be acting to provide cytoprotection during myocardial ischemia and reperfusion.
Kilgore
K S
KS
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Homeister
J W
JW
Satoh
P S
PS
Lucchesi
B R
BR
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000209:etiology* / Q000517:prevention & control*; D003165:Complement System Proteins / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects; D015773:Enalaprilat / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D011312:Pressure; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D008625:Tiopronin / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D003165:Complement System Proteins; D002216:Captopril; D008625:Tiopronin; D015773:Enalaprilat