Effects of losartan on warfarin-induced vascular calcification in rats

Abstract

Objective To investigate the effects and mechanism of losartan regulating vascular calcification in rat vascular calcification models induced by warfarin. Methods Twenty eight 5-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups: Control (C), Model (M), Model+ Low losartan (M+ L), Model+ High losartan (M+ H). Vascular calcification was confirmed by HE and Alizarin Red staining to observe morphology and calcium deposition of vascular wall.The expression of Connexin43 (Cx43) mRNA was detected by real-time quantitative PCR.The expression of mitogen-activated protein kinase (MAPK), Cx43 and Matrix Gla Protein (MGP) were analyzed by western blot. Results The vascular calcification could be induced by warfarin in rats.Compared with C group, The expressions of Cx43 mRNA and protein in aorta in model group were up-regulated significantly (3.98±0.65 vs.1.06±0.31, P<0.01; 1.91±0.45 vs.1.03±0.07, P=0.029). Meanwhile, the extracellular signal-regulated kinase (ERK) activity was significantly increased (1.40±0.19 vs.1.04±0.04, P=0.032) and the expression of MGP was significantly decreased (0.19±0.07 vs.1.00±0.02, P<0.01). Compared with M group, the expression of Cx43 mRNA and protein of aorta in M+ L and M+ H group were down-regulated significantly (2.28±0.47 vs.3.98±0.65, P=0.021; 1.07±0.24 and 0.64±0.24 vs.1.91±0.45, P=0.047 and 0.013) and ERK activity was significantly decreased (0.76±0.04 and 0.69±0.09 vs.1.40±0.19, both P<0.01). Meanwhile, the expression of MGP was significantly increased (0.45±0.08 and 0.83±0.10 vs.0.19±0.07, P=0.013 and P<0.01). Conclusions Warfarin-induced vascular calcification in rats could be suppressed by losartan.The mechanism may be related with inhibition of Cx43 expression and ERK activation, and increased MGP expression. Key words: Losartan; Vascular calcification; Connexin 43; Extracellular signal-regulated MAP kinases; Matrix gla protein