The effect of nifedipine on ischemia-induced changes in the biochemical properties of isolated sarcolemmal vesicles and the ultrastructure of myocardium.
To investigate whether slow Ca2+ channel blockers protect against development of changes in properties of the sarcolemma and in the tissue ultrastructure during myocardial ischemia, nifedipine was administered prior to occlusion (up to 3 hours) of the left anterior descending coronary artery in anesthetized pigs. Intravenous doses which reduced arterial blood pressure by 20-25%, had no effect on the time-dependent reduction of Ca2+-calmodulin and cyclic AMP-dependent 32P incorporation into sarcolemmal phospholamban-like protein. Nifedipine blocked the reduction in the activity of sarcolemmal 5'-nucleotidase. Nifedipine had no significant effect on the long-chain fatty acylcarnitine accumulation in sarcolemma. A marked delay in the appearance of ultrastructural indicators of irreversible tissue injury in subepicardial myocardium was observed, when nifedipine was infused. Particularly the reduced appearance of electron-dense bodies in mitochondria suggested a reducing effect of nifedipine on cellular net gain of Ca2+. Apparently, ischemia-induced loss of the ability of the proteinkinases to incorporate phosphate into sarcolemmal phospholamban-like protein is not a process secondary to Ca2+ overload of the myocardium. The involvement of accumulation of long-chain fatty acylcarnitine within the sarcolemma may also be excluded. The membrane defect as indicated by a change in phosphorylation-mediated control of Ca2+ transport may itself be associated with the development of ischemia (-reperfusion)-induced Ca2+ overload.
D015720:5'-Nucleotidase; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002147:Calmodulin / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D004341:Drug Evaluation; D008929:Mitochondria, Heart / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000648:ultrastructure*; D009543:Nifedipine / Q000494:pharmacology*; D009708:Nucleotidases / Q000032:analysis; D012508:Sarcolemma / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D000099211:Phospholamban
D015720:5'-Nucleotidase; D002118:Calcium; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D000242:Cyclic AMP; D009543:Nifedipine; D009708:Nucleotidases; D000099211:Phospholamban