Inhibition of the renin-angiotensin system has been shown to prevent left ventricular remodeling after myocardial infarction. However, the effect of angiotensin on the signal transduction pathway of left ventricular remodeling after myocardial infarction is as vet unknown. The purpose of this study was to measure myocardial MAPKs and AP-1, NF-kappaB, and Sp-1 DNA-binding activities after myocardial infarction. Moreover. we evaluated the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on signal transduction pathway. Myocardial infarction was produced by ligation of the coronary artery in Wistar rats. Temocapril (ACE inhibitor) (3 and 30 mg/kg/day) and candesartan cilexitil (ARB) (1 and 10 mg/kg/day) were orally administered once a day. After ligation of the left descending coronary artery, JNKs (p46JNK and p55JNK) increased to 2.0-(P<0.01) and 2.8-fold (P<0.01) at 7 days, respectively. ERKs (p44ERK and p42ERK) and p38 activities did not increase significantly AP-1 and NF-kappaB binding activities increased at 5 days, reached their peal; 2.2- and 2.0-fold at 7 days. Sp-1 did Hot change. ACE inhibitor and ARE inhibited JNKs, NF-kappaB and AP-1 activities. Increased JNKs, AP-1, NF-kappaB, and Sp-1 DNA-binding activities were suppressed by both drugs in the infarcted region. Doppler-echocardiography showed that ACE inhibitor and ARE prevented the dilatation of left ventricular cavity at 14 days and improved diastolic filling pattern. JNKs. AP-1 and NF-kappaB activation in myocardial infarcted rats could be responsible for left ventricular remodeling after myocardial infarction and angiotensin mag be related to the activation of these signals. (C) 2001 Academic Press.