培哚普利抑制充血性心力衰竭大鼠心脏合成醛固酮及其合成酶基因的表达

目的　评价血管紧张素转换酶抑制剂培哚普利长期应用对充血性心力衰竭大鼠心脏合成醛固酮的影响。方法　雄性Wistar大鼠结扎左冠状动脉前降支 ,制成充血性心力衰竭模型 ,用培哚普利处理 2 0周 ,以假手术大鼠和未处理的心肌梗死后充血性心力衰竭大鼠作对照 ,离体灌注大鼠心脏 ,灌注液经反向高效液相色谱法纯化 ,放射免疫法检测醛固酮 ,用逆转录聚合酶链式反应检测非梗死心肌醛固酮合成酶基因CYP11B2mRNA的表达情况。结果　心力衰竭组离体心脏灌注液中醛固酮 (10 77.7± 39.9)mg h水平明显高于假手术组 (5 0 0 .3± 2 0 .6 )mg h ,心肌CYP11B2mRNA表达增加 ;培哚普利治疗组不能使血浆AngⅡ (16 0 .5± 12 .1)mg ml、醛固酮 (2 6 2 .0± 18.9)mg ml水平明显降低 ,但是可以明显降低离体心脏灌注液中AngⅡ (112 .1± 16 .5 )mg h和醛固酮 (799.9± 6 3.4 )mg h水平 ,抑制非梗死心肌CYP11B2mRNA的表达增加。结论　充血性心力衰竭时 ,大鼠心脏局部合成醛固酮增加 ,长期应用培哚普利可以抑制心力衰竭大鼠心脏局部醛固酮的合成和CYP11B2表达

Perindopril inhibits aldosterone biosynthesis and CYP11B2 mRNA expression in heart of rats with congestive heart failure

Objective To evaluate the potential action of perindopril,an angiotensin converting enzyme inhibitor, on congestive heart failure rats after myocardial infarction. Methods Male Wistar rats with infarction induced congestive heart failure were treated with perindopril (3 mg/kg per day).Rats with untreated chronic heart failure and sham operated rats were used as positive and normal controls. By means of ex vivo heart perfusion, HPLC, radioimmunoassay and RT PCR,the levels of angiotensin Ⅱ, aldosterone and CYP11B2 gene expression in hearts of the rats were measured.Results Aldosterone production was increased in the heart perfusates of the rats with infarction induced chronic heart failure rats (1?077.7±39.9 mg/h) as compared with that of the sham operated rats(500.3±20.6 mg/h), and CYP11B2 gene expression was enhanced in the noninfarction myocardium. Although perindopril could not inhibit the increases in Ang Ⅱ and aldosterone in plasma,it decreased the levels of Ang Ⅱ and aldosterone in the heart perfusates and inhibited the CYP11B2 gene expression in the noninfarction myocardium. Conclusions Production of aldosterone was increased in the hearts of congestive heart failure rats. Long term perindopril treatment did inhibit aldosterone production in the heart of chronic heart failure rats.