Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril.
We have examined the changes in quantity and activity of cardiac sarcolemmal (SL) phosphoinositide-phospholipase C (PLC)-beta(1), -gamma(1), and -delta(1) in a model of congestive heart failure (CHF) secondary to large transmural myocardial infarction (MI). We also instituted a late in vivo monotherapy with imidapril, an ANG-converting enzyme (ACE) inhibitor, to test the hypothesis that its therapeutic action is associated with the functional correction of PLC isoenzymes. SL membranes were purified from the surviving left ventricle of rats in a moderate stage of CHF at 8 wk after occlusion of the left anterior descending coronary artery. SL PLC isoenzymes were examined in terms of protein mass and hydrolytic activity. CHF resulted in a striking reduction (to 6-17% of controls) of the mass and activity of gamma(1)- and delta(1)-isoforms in combination with a significant increase of both PLC beta(1) parameters. In vivo treatment with imidapril (1 mg/kg body wt, daily, initiated 4 wk after coronary occlusion) improved the contractile function and induced a partial correction of PLCs. The mass of SL phosphatidylinositol 4,5-bisphosphate and the activities of the enzymes responsible for its synthesis were significantly reduced in post-MI CHF and partially corrected by imidapril. The results indicate that profound changes in the profile of heart SL PLC-beta(1), -gamma(1), and -delta(1) occur in CHF, which could alter the complex second messenger responses of these isoforms, whereas their partial correction by imidapril may be related to the mechanism of action of this ACE inhibitor.
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Departments of Human Anatomy and Cell Science and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada R2H 2A6.
P S
PS
Tappia
S Y
SY
Liu
S
S
Shatadal
N
N
Takeda
N S
NS
Dhalla
V
V
Panagia
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D007527:Isoenzymes; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects* / Q000201:enzymology*; D010738:Type C Phospholipases / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D007527:Isoenzymes; C065166:imidapril; D010738:Type C Phospholipases