The Profective Effects And Mechanisms Of Simvastatin On The Left Ventricular Remodeling In Renal Hypertensive Rats

Objective More and more evidences established that statins, HMG-CoA reductase inhibitors, not only effectively reduced serum cholesterol level, but also exerted pleiotropic beneficial effects on cardiovascular disease independent of cholesterol reduction. The adaptive process, particularly left ventricular remolding, happens under long-term internal and external bloodstream stress and stimulation of neuroendocrine hormone, involving increase in left ventricular wall, ventricular expansion and interstitial fibrosis. In addition to increasing blood pressure, imbalance of cell proliferation and apoptosis, intracellular Ca2+ concentration, inflammation , and disorder of vasoactive factors have been identified as the major mechanisms for the control of ventricular remolding. Recently, much attention about the effect of statins on the left ventricular remodeling and its possible mechanisms has been taken by more and more people. The purpose of this study is to investigate the effect of simvastatin and captopril on the left ventricular remodeling and other related factors using two kidney-one clamp renovascular hypertensive rats , trying to discuss the effect of simvastatin on the left ventricular remodeling and further explore the underlying mechanisms involved.Methods The successful rat models induced by two kidney-one clamp method were randomly divided into following four groups for 8 weeks: captopril group(C group,n=6),simvastatin group(S group,n=8),captopril plus simvastatin group(C+S group,n=8)and control group without any therapy(H group,n=6).6 rats of the same age that were operated to expose renal artery without clamping were used as sham operation group (Sh group,n=6).8 weeks later, the rats were measured systolic blood pressure(SBP) using the noninvasive tail-cuff method. After weighting, the rats were sacrificed, related samples were collected and studied as follow:①The serum lipids levels were detected using common enzyme practice.②The plasma free 8-F2αisoprotanes was performed by enzyme linked immunosorbent assay.③T he level of angiotensinⅡin plasma and left ventricular tissue was determined by radioimmunoassay.④The serum nitric oxide was evaluated by nitrate reductase enzyme practice.⑤Myocardium collagen concentration was determined by colorimetric method.⑥Scaled left ventricular weight , then calculated the left ventricular weight index.⑦Paraffin section of heart,HE staining,the microstructure was studied.Results No significant differences were noted between values for each treatment group.During the experiment,we found: The left ventricular remodeling in renal hypertensive rats is associated with decreased NO concentration and increased plasma 8-F2αisoprotanes production linked to the upregulation of angiotension. Also,we found: 1. The left ventricular weight index(4.03±0.81mg/g vs 1.61±0.45 mg/g, P<0.01)and collagen concentration of hypertnsive rats (5.05±0.73ug/mg vs 2.90±1.04ug/mg, P<0.01)were both higher than sham operation group.2. The left ventricular weight index(2.95±1.36mg/g vs 4.03±0.81mg/g, P<0.05)and collagen concentration(4.32±0.43ug/mg vs 5.05±0.73ug/mg, P<0.01)of simvastatin group were both lower than hypertnsive rats.3. The left ventricular weight index(1.92±0.72 mg/g vs 4.03±0.81mg/g, P<0.01)and collagen concentration (3.59±0.68ug/mg vs 5.05±0.73ug/mg, P<0.01)of captopril group were both lower than hypertnsive rats.4. The left ventricular weight index(2.95±1.36mg/g vs 1.92±0.72 mg/g, P<0.05)and collagen concentration(4.32±0.43ug/mg vs 3.59±0.68ug/mg, P<0.05)of simvastatin group were both higher than that of captopril group.5. There was no difference in the left ventricular weight index between captopril group and captopril plus simvastatin group(1.58±0.78mg/g vs 1.92±0.72mg/g, P>0.05). But the collagen concentration of captopril group is higher than that of the captopril plus simvastatin group(2.96±0.33ug/mg vs 3.59±0.68ug/mg,P<0.05).Conclusions 1. The intake of captopril can ameliorate left ventricular remodeling process.2. The intake of simvastatin can ameliorate left ventricular remodeling process.3. The effects of simvastatin on left ventricular remodeling process are less potent than those of captopril group.4.Captopril plus simvastatin has potentially beneficial effects on left ventricular remodeling than captopril group.