Subcellular and molecular mechanisms of the effects of cardiac glycosides and angiotensin-converting enzyme inhibitors on contractile function and energy conversion in myocardial myofibrils under normal conditions and during acute cardiac insufficiency.
Experiments on skinned and hybrid myocardial fibers isolated from normal dogs and animals subjected to 120-min occlusion of the anterior interventricular branch of the coronary artery showed that in contrast to cardiac glycosides, angiotensin-converting enzyme inhibitors suppress contractile ability of myocardial myofibrils in a dose-independent manner within the concentration range of 10(-12)-10(-4)M. This effect is accompanied by a decrease in fiber relaxation rate most pronounced in the presence of captopril. Actin, the major protein of fine filaments is the target for b-acetyldigoxin, K-strophanthin, captopril, enalapril, and trandolapril in myocardial myofibrils. During coronary occlusion, the inhibitors of angiotensin-converting enzyme induce structural and conformational changes in actin that decrease efficiency of contraction. The data obtained cast doubt on advisability of therapeutic use of angiotensin-converting enzyme inhibitors in the therapy of myocardial infarction, especially in its early period.
Sukoyan
G V
GV
Research Center of Medical Biophysics and Application of New Biomedical Technologies, Georgian Ministry of Health, Tbilisi.
Karsanov
V N
VN
Tatulashvili
D R
DR
Gochua
E I
EI
Samsonidze
T G
TG
Karsanov
N V
NV
D000199:Actins / Q000737:chemistry; D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002301:Cardiac Glycosides / Q000037:antagonists & inhibitors*; D004285:Dogs; D004734:Energy Metabolism; D066298:In Vitro Techniques; D008958:Models, Molecular; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects* / Q000378:metabolism; D011487:Protein Conformation
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D002301:Cardiac Glycosides