EFFECT OF COMBINATION TREATMENT USING RAMIPRIL AND IRBESARTAN ON LAMININ ALPHA 2 CHAIN AND APOPTOSIS IN THE LEFT VENTRICULAR MYOCARDIUM OF SPONTANEOUSLY HYPERTENSIVE RATS.

Abstract

Objective: Deficiency of laminin α-2 chain, so called merosin, is known to be a cause of congenital muscular dystrophy. The present study is to address whether modulation of renin angiotensin system influence on laminin α-2 expression and apoptosis in left ventricular myocardial tissue by treating spontaneously hypertensive rat with Ramipril and Irbesartan. Design and Methods : Group was designed; negative control(n=5, Wistar-Kyoto rat), positive control(n=6, SHR), group I(n=6, SHR on Ramipril), group II(n=6, SHR on Irbesartan), group III(n=6, SHR on Ramipril + Irbesartan). After six week period, the level of laminin α-2 expression with immunohistochemistry and with RT-PCR and apoptosis in the left ventricular myocardium. Results: --------------------------------------------------------------------------------------- Group Immuno reactivity mRNA expression Apoptosis --------------------------------------------------------------------------------------- WKY control + + ± SHR control + ++ + Group I(Ramipril) ++ ++ ++ Group II(Irbesartan) + + ++ Group III(combination) ± + ± --------------------------------------------------------------------------------------- ±, trace; +, weak; ++, moderate. 1) Group III showed markedly diminished induction of immunoreactivity of laminin α-2. 2) Induction of laminin α-2 mRNA was not evident in group II and group III. 3) Apoptotic nuclei were much less frequent in group III. Conclusions: Laminin α-2 expression was evident in left ventricular myocardium of SHR, which is diminished by Ramipril or Irbesartan. Co-administration of two drugs decreased laminin α-2 level most strikingly. It suggests that administration of both drug is much more protecive for left ventricular myocardium. (This study is supported by the 2004 research grant of Korean Society of Hypertension)