The effect of a calcium channel antagonist, Nisoldipine, on the ischemia-induced change of canine sarcolemmal membrane.
Ischemic injury was produced in the dog heart by occluding the left anterior descending coronary artery just below the second diagonal branch for a duration of 1.5 h followed by the release of occlusion. Nisoldipine, 3.5 micrograms/kg was injected intravenously 10 min before the occlusion and again 10 min before the commencement of reperfusion. The activity of serum creatine phosphokinase greatly increased after the reperfusion, and this increase was significantly suppressed by Nisoldipine. This drug, in addition, prevented ischemia-induced myocardial hemorrhage and premature ventricular contraction. Sarcolemmal membrane vesicles were prepared from an ischemic and non-ischemic portions of the myocardium 3 h after the commencement of reflow. The fraction was purified approximately 12-fold with respect to ouabain-sensitive (Na+K+)-ATPase as an indicator; contamination of mitochondria was minimum with cytochrome c oxidase as an indicator. Without treatment of Nisoldipine, the total amount of sarcolemmal phospholipid obtained from the ischemic area, as well as the amounts of phosphatidyl-choline and phosphatidyl-ethanolamine, were significantly decreased as compared with those obtained from the non-ischemic area. Nisoldipine treatment abolished the decrease in the sarcolemmal phospholipids, total as well as phosphatidyl-choline and -ethanolamine, induced by ischemia plus reperfusion. Therefore, our work indicates that the Ca++ channel antagonist, Nisoldipine, suppresses the ischemia-induced increase in phospholipid breakdown of cardiac sarcolemma probably through its inhibitory effect on the Ca++-mediated activation of membrane phospholipase, through its vasodilatory action, or both.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy* / Q000201:enzymology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009543:Nifedipine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D015737:Nisoldipine; D010743:Phospholipids / Q000032:analysis; D011725:Pyridines / Q000008:administration & dosage*; D012508:Sarcolemma / Q000187:drug effects* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002121:Calcium Channel Blockers; D010743:Phospholipids; D011725:Pyridines; D015737:Nisoldipine; D003402:Creatine Kinase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine