Angiotensin blockade inhibits increased JNKs, an-1 and NF-kappa B RNA-binding activities in myocardial infarcted rats

Inhibition of the renin-angiotensin system has been shown to prevent left v entricular remodeling after myocardial infarction. However, the effect of a ngiotensin on the signal transduction pathway of left ventricular remodelin g 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 a ctivities after myocardial infarction. Moreover. we evaluated the effects o f angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor bl ocker (ARB) on signal transduction pathway. Myocardial infarction was produ ced by ligation of the coronary artery in Wistar rats. Temocapril (ACE inhi bitor) (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 desce nding coronary artery, JNKs (p46JNK and p55JNK) increased to 2.0-(P<0.01) a nd 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 ac tivities increased at 5 days, reached their peal; 2.2- and 2.0-fold at 7 da ys. Sp-1 did Hot change. ACE inhibitor and ARE inhibited JNKs, NF-kappaB an d AP-1 activities. Increased JNKs, AP-1, NF-kappaB, and Sp-1 DNA-binding ac tivities were suppressed by both drugs in the infarcted region. Doppler-ech ocardiography 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 Ac ademic Press.