ANGIOTENSIN-II TYPE 1-RECEPTOR ANTAGONIST CANDESARTAN CILEXITIL PREVENTS LEFT-VENTRICULAR DYSFUNCTION IN MYOCARDIAL INFARCTED RATS

The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricul ar systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performe d Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, le ft ventricular end-diastolic dimension increased (Control, 6.2+/-0.6 m m; MI, 8.7+/-0.6 mm; P<0.01), fractional shortening decreased (Control , 41+/-5%; MI, 16+/-3%; P<0.01) and E wave deceleration rate increased (Control, 14.3+/-2.0 m/sec(2); MI, 23.3+/-2.3 m/sec(2); P<0.01). Cand esartan cilexitil significantly prevented these changes. The mRNA expr essions of beta-myosin heavy chain, alpha-skeletal actin, atrial natri uretic peptide, and collagens I and III in the non-infarcted left vent ricle and right ventricle were increased at four weeks and were signif icantly suppressed by treatment with candesartan cilexitil. At four we eks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic ret iculum Ca2+-ATPase mRNA expression in the infarcted region including t he adjacent non-infarcted left ventricle and right ventricle were decr eased and candesartan cilexitil restored it to the control level. Cand esartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.