2005•中华医学杂志：英文版Requires access
Combined effects of ramipril and angiotensin II receptor blocker TCV116 on rat congestive heart failure after myocardial infarction
TAOZe-wei, HUANGYuan-wei, XIAQiang, XUQi-wen
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Abstract
Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI). Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), B-type natriuretic peptide (BNP), transforming growth factor-β1 (TGF-β1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated. Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of c