Inhibition Effect Of Losartan On Ventricular Remodeling By Affecting Cardiac Fibroblasts Of Myocardium In Hypertensive Rats

Objective To investigate inhibition effect of losartan on ventricular remodeling by affecting cardiac fibroblasts of myocardium in hypertensive rats.Methods Sprague-Dawley rats (220-250g) were used to set up the two kidney oneclipped Goldblatt hypertensive rats (2K1C). The rats were randomly divided into control group, hypertensive group and losartan treatment group (losartan 20 mg/kg for 6 weeks). Systolic blood pressure (SBP) was recorded, once a week , using the tail-cuff method. The ratio of heart weight (HW) and body weight (BW) was calculated . The expression of matrix metalloproteinases-2, collagen III and JNK1/2 was determined by immunohistochemistry. Neonatal rat cardiac fibroblasts were cultured. The cells viability was determined by MTT. To determine effects of Ang II on JNK1/2 activity, cells were incubated (for 0, 2, 5, 10, 30, 60, 120 min) in serum-free media with Ang II, then Fibroblasts were exposed to serum-free media with or without Ang II and losartan (Ang II100 nM, Ang II100 nM+1osartan 100 nM,losartan 100 nM,losartan for 45min before), media of cell cultrue was collected,cells protein was collected with MBST buffer. The relative abundance of MMP-2 and JNK in cells was determined by immunoblotting. The secretion of MMP-2 in media of cell culture was determined by ELISA .Result In 2K1C rats, SBP was significantly raised compared with control group (p< 0.05), and The ratio of HW and BW was increased. The expression of MMP-2,...