ALTERATIONS IN SARCOPLASMIC-RETICULUM AND ANGIOTENSIN-II TYPE-1 RECEPTOR GENE-EXPRESSION AFTER MYOCARDIAL-INFARCTION IN RATS

The purpose of this study was to investigate the function of sarcoplas mic reticulum (SR) and the role of angiotensin ZI type 1 receptor (AT1 ) in ventricular remodeling in non-infarcted areas after myocardial in farction (MI). MI was produced in anesthetized Sprague-Dawley rats (10 -12 weeks old) by ligation of the left anterior descending coronary ar tery. Four weeks after MI, hemodynamic measurements were performed. SR Ca2+ ATPase activity and mRNA (SERCA2a) and AT1 mRNA (AT1a, AT1b) wer e analyzed. Left ventricular end-diastolic pressure was higher and lef t ventricular dp/dt was significantly lower in the MI group. In non-in farcted areas in the MI group, myocardial transverse diameter was sign ificantly greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b mRNA expression level was unchanged. Th ese results suggest that, in the ventricular remodeling after MI, alte rations in SR protein and its mRNA in non-infarcted myocardium help in itiate heart failure and that Ca overload caused by the up-regulation of AT1a mRNA is an important cause of alteration in SR function.