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 sarcolemma l (SL) phosphoinositide-phospholipase C (PLC)-beta(1), -gamma(1), and -delt a(1) in a model of congestive heart failure (CHF) secondary to large transm ural myocardial infarction (MI). We also instituted a late in vivo monother apy with imidapril, an ANG-converting enzyme (ACE) inhibitor, to test the h ypothesis that its therapeutic action is associated with the functional cor rection of PLC isoenzymes. SL membranes were purified from the surviving le ft; 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 exami ned in terms of protein mass and hydrolytic activity. CHF resulted in a str iking 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 fu nction and induced a partial correction of PLCs. The mass of SL phosphatidy linositol 4,5-bisphosphate and the activities of the enzymes responsible fo r its synthesis were significantly reduced in post-MI CHF and partially cor rected by imidapril. The results indicate that profound changes in the prof ile of heart SL PLC-beta(1), -gamma(1), and -delta(1) occur in CHF, which c ould alter the complex second messenger responses of these isoforms, wherea s their partial correction by imidapril may be related to the mechanism of action of this ACE inhibitor.