福辛普利和左旋氨氯地平对高盐饮食下自发性高血压大鼠SBP、左心室肥厚、NO及ET-1水平的影响

Fosinopril and Levoamlodipine Impact SBP,LVH,NO and ET-1 Levels Under High-salt Diet in SHR

目的观察福辛普利和左旋氨氯地平对高盐饮食下自发性高血压大鼠(SHR)收缩压(SBP)、左心室肥厚(LVH)、一氧化氮(NO)及内皮素-1(ET-1)水平的影响。方法将40只8周龄SHR随机分为5组(n=8),即对照组、高盐对照组、福辛普利组、左旋氨氯地平组及联合治疗组。除对照组给予含0.9%氯化钠饲料喂养外,其余4组大鼠均给予含4%氯化钠饲料喂养8周。在第5周起各组按照0.01 mL.g-1等体积0.9%氯化钠灌胃4周。福辛普利组:按剂量4 mg.kg-1.d-1;左旋氨氯地平组:按剂量1 mg.kg-1.d-1;联合治疗组:福辛普利4 mg.kg-1.d-1,左旋氨氯地平1 mg.kg-1.d-1。每周测量SBP、体质量、心率1次,8周后通过放血处死全部SHR,计算左心室质量指数(LVMI),放免法测定血清及心肌ET-1含量,化学法检测血清及心肌NO水平。结果与高盐对照组比较,左旋氨氯地平组能明显降低高盐饮食下SHR的SBP,增加血清NO的含量,减少心肌组织ET-1含量和LVMI(均P<0.01);福辛普利组能明显降低高盐饮食下SHR心肌组织ET-1含量和LVMI(P<0.05或P<0.01),但无明显降低SBP作用;联合治疗组能更明显降低SBP和LVMI(均P<0.01)。结论左旋氨氯地平与福辛普利均能降低高盐饮食下SHR SBP作用,机制可能与血清NO含量的升高有关;抑制LVH的作用机制可能与心肌组织ET-1含量降低有关。

Objective To observe Fosinopril and Levoamlodipine impact of systolic blood pressure（SBP）,left ventricular hypertrophy（LVH）,nitric oxide（NO） and endothelin-1（ET-1） levels under high-salt diet in spontaneously hypertensive rats（SHR）.Methods Forty 8-wek-old SHRs were randomly divided into five groups（n=8）,namely,SHR control group,high-salt SHR control group,fosinopril group,Levoamlodipin group,combinative therapy group.SHR control group were fed with 0.9% NaCl diet,the rats in remaining four group were treated with 4% NaCl diet for 8 weeks.All groups were given by intragastric administration with 0.9% NaCl 0.01 mL·g-1 once a day since the first 5 week.Fosinopril group（4 mg·kg-1·d-1）,Levoamlodipin group（1 mg·kg-1·d-1）,combinative therapy group（Fosinopril,4 mg·kg-1·d-1＋Levoamlodipine,1 mg-1·kg-1·d-1）.SBP,body weight（BW）and heart rate were measured once a week.After 8 weeks all SHR were killed by bleeding.Left ventricle mass index（LVMI）were examixned.ET-1 levels were measured by radioimmunoassay and NO levels were measured by the chemical assay in plasma and cardiac muscle.Results Compared with high-salt SHR control group,In Levoamlodipin group SBP,ET-1 levels of the cardiac muscle and LVMI,can be reduced under high-salt diet,while plasma NO levels can be elevated（all P0.01）;In fosinopril group ET-1 levels of the cardiac muscle and LVMI can be reduced under high-salt diet（P0.05 or P0.01）,but no significant changes were found in SBP;In combined treatment group SBP and LVMI can be significantly reduced（all P0.01）.Conclusion Mechanism of the two kinds of medication to reduce SBP may be associated with plasma NO levels elevated,and control of LVH may be related to myocardial tissue ET-1 levels decreased.