Effects of phospholipase inhibitors and calcium antagonists on the changes in myocardial phospholipids induced by isoproterenol.
To investigate the change in myocardial phospholipids after the administration of isoproterenol and its prevention by pretreatment with phospholipase inhibitors and calcium antagonists, we determined the phospholipid species in the heart of female Wistar rats. Isoproterenol (40 mg/kg) was administered 24 h before excising the heart, and chlorpromazine, mepacrine (phospholipase inhibitors), nifedipine, verapamil (calcium antagonists) and propranolol (beta-adrenoceptor blocker) were injected intraperitoneally 30 min prior to isoproterenol administration. The phospholipid species were quantified using silica gel precoated thin-layer rods and the hydrogen flame ionization method. Isoproterenol induced significant increases in heart/body weight ratio, myocardial protein/heart weight ratio and lysophosphatidylcholine (LPC), and significant decreases in myocardial total phosphorus, creatine kinase (CK) activity, phosphatidylethanolamine and phosphatidylcholine (PC). The significant decrease in PC and increase in LPC indicated the degradation of myocardial phospholipids. Pretreatment with nifedipine (30 mg/kg), verapamil (50 mg/kg) or propranolol (20 mg/kg) completely prevented the occurrence of myocardial injury through the preservation of myocardial phospholipid composition, total phosphorus, CK activity and heart/body and protein/heart weight ratios. On the other hand, chlorpromazine (30 mg/kg) and mepacrine (50 mg/kg) partially prevented myocardial damage through the preservation of myocardial phospholipid composition, total phosphorus and CK activity. Results suggest that not only calcium influx but also phospholipase activation plays an important role in the development of myocardial injury induced by isoproterenol.
Takasu
N
N
Department of Internal Medicine 2, Nagoya University School of Medicine, Japan.
Hashimoto
H
H
Miyazaki
Y
Y
Ito
T
T
Ogawa
K
K
Satake
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010743:Phospholipids / Q000302:isolation & purification*; D011433:Propranolol / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil
D002121:Calcium Channel Blockers; D010743:Phospholipids; D011433:Propranolol; D014700:Verapamil; D010740:Phospholipases; D011796:Quinacrine; D009543:Nifedipine; D007545:Isoproterenol; D002746:Chlorpromazine