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Korean Circ J. 2002 Aug;32(8):680-688. Korean. Original Article.
Chang K , Baek SH , Ko SH , Yoon KH , Kim KY , Seung KB , Chae JS , Kim JH , Hong SJ , Choi KB .
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Pathology, College of Medicine, Wonkwang University, Iksan, Korea.

BACKGROUND AND OBJECTIVES: Coronary microvascular remodeling is one of the complications associated with diabetic cardiovascular disease. We investigated the effect of long-term treatment with ramipril, an angiotensin converting enzyme inhibitor, on coronary microvascular remodeling on a type II diabetic model, the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. MATERIALS AND METHODS: Twenty OLETF diabetic, and twenty LETO non-diabetic rats at twenty-four weeks old, were randomized into 4 equal groups for treatment with either an aqueous solution of ramipril (5 mg/kg, n=10 for two groups) or saline (n=10 for two groups) for 24 weeks on a daily basis. The blood glucose levels, body weights and blood pressures of the rats were checked on a regular basis. Masson's trichrome and picrosirius red stains were used for the morphometric analysis of the thickening of the coronary arterial wall and the degree of perivascular fibrosis. The myocardial collagen content was determined by measuring the levels of myocardial hydroxyproline. RESULTS: Marked thickening of the coronary microvascular wall and prominent perivascular fibrosis were detected in the hearts of OLETF rats to a greater extent than in the LETO rats (p<0.01). Ramipril significantly prevented coronary microvascular remodeling in OLETF rats (p<0.01), but there was no significant difference in the collagen content/dry heart weight ratio between the groups. CONCLUSION: Long-term treatment with ramipril has an antifibrotic effect, and improves the coronary microvascular remodeling in diabetic OLETF rats.

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