Effect of Ramipril, Irbesartan and combination treatments on laminin alpha 2 chain expression and apoptosis in the aortic smooth muscle layer of spontaneously hypertensive rats.

Abstract

Objective: Deficiency of laminin α-2 chain, so called merosin, is known to be associated with cardiomyopathy or congenital muscular dystrophy. The Aim of this study is to investigate the effect of Ramipril, Irbesartan, and combination treatment on the expression of laminin α-2 and apoptosis in the aortic smooth muscle layer of spontaneously hypertensive rats. Design and Methods : Five Wistar-Kyoto rats(WKY) were assigned to negative control. SHRs were assigned to positive control(n=6), group I(n=6, Ramipril treated), group II(n=6, Irbesartan treated), group III(combination). After a six week period, the expression of laminin α-2 with immunohistochemistry and with in situ RT-PCR and the apototic activity were assessed in the muscle layer of the aorta. Results: Group Immunoreactivity mRNA expression Apoptosis --------------------------------------------------------------------------------------- WKY control + + - SHR control +++ ++ ++ Group I(Ramipril) ++ ++ ++ Group II(Irbesartan) ++ + + Group III(combination) + ± ± -------------------------------------------------------------------------------------- ±, trace; +, weak; ++,moderate; +++, strong. 1) Weakened induction of laminin α-2 chain expressions were observed in group I, group II, and group III. 2) Induction of laminin α-2 mRNA was not detectable in group II and group III, which were similiar to the negative control. 3) Apoptotic nuclei were much less frequently observed in group III. Conclusions: Laminin α-2 expression was evdent in the aortic smmooth muscle layer of SHR, which is diminished by Ramipril or Irbesartan. Combination treatment resulted in marked decrease of the laminin α-2 expression. It implies that combination treatment of ramipril and Irbesartan is much more protective for aorta than each drug alone.