Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats

Abstract

Abstract: AIM: To investigate the effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats (SHR).METHODS: SHRs (n=24)were randomly divided into four groups (n=6):SHR control group, 50 mg atorvastatin group (50 mg·kg^-1·d^-1), 10mg atorvastatin group (10 mg·kg^-1 ·d^-1)and valsartan group (20 mg·kg^-1 ·d^-1).Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP)was measured before and after treatment with atorvastatin every 2 weeks.Plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)and Ang ,and myocardial Ang Ⅱ, hydroxyproline and collagen levels were measured.Heart weight (HW), left ventricle mass (LVM)and left ventricle mass index (LVMI)were gauged.Myocardial ultrastructure was observed by transmission electron microscopy.RESULTS: SBP in all SHR groups was much higher than that in WKY group beforeexperiment (P<0.01).SBP significantly decreased in 50 mg atorvastatin group at 4 weeks and 6 weeks (P< 0.01).Compared with SHR control group, there was a significant descent in serum TC, TG and LDL-C concentrations in 50 mg atorvastatin group (P<0.05, or P <0.01).The level of LDL-C decreased merely in 10 mg atorvastatin group (P<0.05).There was no difference in plasma Ang Ⅱ level among WKY group and SHR groups.But myocardial Ang Ⅱ level in SHR group was significantly higher than that inWKY group (P<0.05). After 6 weeks, plasma Ang Ⅱ level among atorvastatin groups and valsartan group was markedly higher than that in SHR control group (P<0.01), and myocardial Ang Ⅱ level was significantly lower than that in SHR group (P<0.05).Myocardial hydroxyproline and collagen level in SHR group was significantly higher than that in WKY group (P<0.01).After treatment of 50 mg atorvastatin, it was markedly lower than that in SHR control group (P<0.05).Compared with WKY group, HW, LVM and LVMI were significantly increased in SHR group (P<0.01).After treatment of 50 mg atorvastatin, HW, LVM and LVMI were significantly lower than those in SHR control group (P<0.05).The changes of myocardial ultrastructure in atorvastatin and valsartan groups were significantly improved.CONCLUSION: Atorvastatin can significantly improve ventricular remodeling in SHR, and decrease blood pressure and myocardial Ang Ⅱ level which may be one of its mechanisms.

Key words: atorvastatin, spontaneously hypertensive rats, hypertension, ventricular remodeling, angiotensin Ⅱ, hydroxyproline

CLC Number:

R965
R972.4

WANG An-Cai, CHENG Bei, XIE Xiao-Jing, XU Hao. Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(8): 880-884.

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