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The Effect of Angiotensin Receptor Blocker on the Myocardial Fibrosis in Animal Model of Adriamycin Induced Cardiomyopathy
가톨릭대학교 의과대학 순환기내과¹ , 생화학교실²
정우백¹, 윤호중¹ ,윤정숙 ¹ ,최윤석¹ ,임상현¹ ,박철수¹ ,정해억¹ ,장기육¹ ,오용석¹ ,정욱성¹ ,이만영¹ ,승기배¹ ,김재형¹ ,이정화²
Background: Previous studies demonstrated that adriamycin (AD) aggravates myocardial fibrosis and suppresses the expression of cardiac ankyrin repeat protein (CARP). We observed the effect of olmesartan (OT), an angiotensin receptor blocker, on the expression of CARP and myocardial fibrosis in AD induced cardiomyopathy. Materials & Methods: 32 Normotensive Wistar-Koyto rats (WKR) and 32 spontaneously hypertensive rats (SHR) were divided into eight groups (AD injected vs. normal saline (NS) injected, placebo vs. OT treated). 2.5mg/kg of AD was injected intraperitonealy twice a week for 3 weeks to four AD treated groups and daily dose of 10 mg/kg OT was administered orally for 6 weeks to four OT treated groups. Blood pressure (BP) was measured before and after OT treatment. Immunohistochemical stain using synthesized CARP antibody and picrosirius stain was performed on left ventricle. The positively stained areas were measured by using an image analysis program (Image Pro-Plus 4.5) and the CARP volume fractions (CaVF) and collagen volume fractions (CVF) were calculated. Results: 1. Systolic BP of WKR was decreased from 121.5±31.4 mmHg to 110.9±15.8 mmHg (p=0.026) and systolic BP of SHR was decreased from 182.5±38.8 mmHg to 124.1±18.5 mmHg (p<0.001) after OMST treatment. 2. The CaVF of OT treated groups were increased significantly in AD injected groups. 3. The CVF of OT treated groups decreased significantly in AD injected groups. (see Figure) Conclusion: OT increases CARP expression in AD induced cardiomyopathy. Increased CARP expression may have a role in reducing myocardial fibrosis, especially in SHR.
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