Abstract: Objective　To investigate the effect of allisartan isoproxil on  stable antihypertension and cardioprotection in spontaneous hypertensive rats (SHR). Methods　Twenty 13-week-old male SHR rats were randomly divided into the model group and the alisartan ester group, with 10 rats in each group. The other 10 male Wistar-Kyoto rats of the same age were used as the control group. The allisartan isoproxil group was administered allisartan isoproxil by gavage continuously for 34 weeks, the model group and the control group were given equal amounts of distilled water. Blood pressure was monitored every four weeks starting at the 16 week. Interventricular septum in diastolem (IVSd), interventricular septum in systole (IVSs), left ventricular posterior wall in diastole (LVPWd), left ventricular posterior wall in systole (LVPWs), end-systolic left ventricular diameter (LVIDs), end-diastole left ventricular diameter (LVIDd), ejection fraction (EF) and left ventricular mass (LVM) were measured by ultrasound at 48 weeks. The animals were then executed and sampled. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe myocardial pathological changes of rat heart. qPCR and Western blot assay were used to detect the mRNA and protein expression of collagen type Ⅰ (Col-Ⅰ), collagen type Ⅲ (Col-Ⅲ), skeletal muscle actin α1 (ACTA1), and platelet response protein (THBS4) in myocardial tissues. Results　Compared with the control group, the blood pressure was significantly higher in the model group (P＜0.05). Compared with the model group, systolic blood pressure and diastolic blood pressure were significantly lower in the allisartan isoproxil group (P＜0.05). Compared with the control group, IVSs, LVPWd, LVM and LVPWs were increased, and LVIDd and EF were decreased in the model group (P＜0.05). Compared with the model group, IVSs, IVSd, LVPWd, LVM and LVPWs were decreased, and LVIDd, LVIDs and EF were increased in the allisartan isoproxil group (P＜0.05). Compared with the control group, myocardial fibers were disordered, blue collagen fibers were deposited and the mRNA and protein expression levels of Col-Ⅰ, Col-Ⅲ, ACTA1 and THBS4 were increased in the model group.  (P＜0.05). Compared with the model group, the myocardial pathological changes were improved, the mRNA and protein levels of Col-Ⅰ, Col-Ⅲ, ACTA1 and THBS4 were decreased in the alisartan isoproxil group (P＜0.05). Conclusion　Allisartan isoproxil can effectively reduce blood pressure in SHR, attenuate the level of myocardial tissue fibrosis due to hypertension, and improve ventricular remodeling and cardiac function.

Key words: rats, inbred SHR, angiotensin Ⅱ, ventricular remodeling, actins, thrombospondins, allisartan isoproxil, ACTA1, myocardial fibrosis