Protective effect of fasudil against left ventricular hypertrophy in rats with pressure overload

Objective: To investigate the effects of fasudil on left ventricular hypertrophy in rats with pressure overload, and its possible mechanism. Methods: Pressure overload model in 42 male 6-week-old SD rats were established by abdominal aorta constriction, and divided into the operation group. Eight healthy rats were set as sham group. Twenty-eight survival abdominal aorta constriction rats after 4 weeks of operation were randomly divided into the model group, high dose fasudil group(FH group) and low dose fasudil group(FL group). After four weeks of drug intervention, the left ventricular mass indexes(LVMI) of all groups were calculated. The myocardial pathological changes were observed. The myocyte diameters(MD) were detected. Myocardial hydroxyproline(HYP) contents were determinated by alkali hydrolysis. Plasma and myocardial AngⅡ concentrations were detected by enzyme linked immunosorbent assay. Myocardial expression levels of phosphorylated myosin phosphatase targeting protein subunit 1(p-MYPT1), matrix metalloproteinase 9(MMP9) and tissue inhibitor of metalloproteinase 1(TIMP1) were analyzed by immunohistochemical staining. Results: Compared with the sham group, myocardial cells hypertrophy and collagen deposition in myocardial interstitium were found, the levels of LVMI, MD, HYP, AngⅡ, p-MYPT1, MMP9 and TIMP1 increased significantly, and the ratio of MMP9/TIMP1 decreased significantly in model group(P<0.01). Compared with the model group, myocardial cells hypertrophy and collagen deposition were improved, and the levels of LVMI, MD, HYP, Ang Ⅱ, p-MYPT1, MMP9, TIMP1 decreased significantly in FH group and FL group(P<0.05 to P<0.01). Conclusions: Fasudil improving left ventricular hypertrophy in pressure overload rats maybe related to the regulating myocardial MMP9 and TIMP1 expression levels