Long acting calcium antagonist amlodipine prevents left ventricular remodeling after myocardial infarction in rats

• Published in: Cardiovascular research 1998-03, Vol.37 (3), p.618-626
• Main Authors: SHIMADA, T, YOSHIYAMA, M, TAKEUCHI, K, OMURA, T, TAKEMOTO, Y, KIM, S, IWAO, H, YOSHIKAWA, J
• Format: Article
• Language: English
• Subjects: Actins - genetics; Amlodipine - therapeutic use; Animals; Antianginal agents. Coronary vasodilator agents; Atrial Natriuretic Factor - genetics; Biological and medical sciences; Blotting, Northern; Calcium Channel Blockers - therapeutic use; Cardiovascular system; Collagen - genetics; Echocardiography; Gene Expression - drug effects; Hemodynamics - drug effects; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - prevention & control; Male; Medical sciences; Myocardial Infarction - complications; Myocardial Infarction - metabolism; Myocardium - metabolism; Myosin Heavy Chains - genetics; Pharmacology. Drug treatments; Rats; Rats, Wistar; RNA, Messenger - analysis; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - prevention & control
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(97)00247-2

The purpose of this study was to examine the effect of amlodipine, a long-acting calcium antagonist, on the left ventricular remodeling, including systolic and diastolic dysfunction, the change of cardiac gene expression in the myocardial infarcted rats (MI). On the first day after myocardial infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or untreated groups (MI; n = 9). We then performed Doppler-echocardiographic examinations and measured the hemodynamics at four weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight of right ventricle in MI was significantly larger than in the control rats (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01) (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01 to MI). The rats in MI showed systolic dysfunction shown by the decreased fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0 m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at four weeks after the myocardial infarction were all significantly suppressed by the treatment with amlodipine. On the other hand, depressed alpha-MHC was restored to normal levels by amlodipine in both regions. Amlodipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.