| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
*Background* It is known that a heart wil be lead to a remodeling when myocardial infarction or pressure overload is present. A myocardial renin-angiotensin system (RAS) is suggested to participate to a genesis of this alteration. A long term treatment of patients with congestive heart failure, main cause of which were myocardial infarction, with angiotensin converting enzyme inhibitor has demonstrated to increase a survival rate in a clinical trial. We evaluated with a molecular biological technique the effects of a inhibition of RAS in experimentally produced myocardial infarctions in rats in this study. *Materials and Methods* A myocardial infarction was produced by a ligation of a left coronary artery at the close to its begining of a male Wistar rat. The heart was isolated at 1 to 12 weeks after the surgery, and the heart was stained with TTC and Evans Blue to devide the tissue into survival or infarcted, then the tissue were provided toevaluate followings ; collagen content, ACE
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activity, angiotensin II receptor binding capacity, mRNA expressions of ACE and angiotensin type 1 receptor (AT1) by a reverse transcriptase polymarase chain reaction (RT-PCR). Rats had been administered with an AT1 blockade of E-4177 (3 or 10 mg/kg/day) or an ACE inhibitor of enalapril (3 or 15 mg/kg/day) daily from the 3 days after the surgery to 12 weeks, then compared with the nontreated rats at the same age. *Results* Heart weight, myocardial collagen content, ACE activity, AT1 receptor binding capacity, and mRNA expressions of ACE and AT1 had been increased in the rats with myocardial infarction from 4 weeks to 12 weeks after the surgery compared with sham operated rats. These alterations were normalized or subnormalized remarkablly with the treatments of high dose E-4177 or enalapril. Although over 3 ml of pleural effusion was found in all nontreated rats with myocardial infarction, there were no rats with such findings in treated myocardial groups. Sarcolemmal Na^+-Ca^<2+> exchange activity was depressed in nontreated myocadial infarcted rats, and this was found to be normalized in treated groups. These alterations were in a same manner as pressure overload cardiac hypertrophy models. Finally, there was no remarkable difference in infarction size between treated and nontreated infarcted rats. *Conclusions* Survived myocardium after myocardial infarction was caused hypertrophy and fibrosis, so called remodelling, and cardiac RAS seemed to concern the genesis of these alterations. It is suggested that the drugs which have anti-RAS action such as an AT1 blockade and an ACE inhibitor will be important to treat the cardiac remodelling after myocardial infarction and congestive heart failure. Less
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