氨氯地平和阿托伐他汀对高血压大鼠血浆及心肌血管紧张肽Ⅱ的影响

Synergistic effect of amlodipine and atorvastatin on myocardial and plasma angiotensin Ⅱ in spontaneously hypertensive rats

目的观察氨氯地平、阿托伐他汀单药和联合用药对自发性高血压大鼠(SHR)循环及心肌血管紧张肽Ⅱ(AngⅡ)的影响,探讨联合用药改善左室肥厚的机制。方法8只雄性Wistar-Kyoto大鼠(WKY大鼠)作为正常血压WKY对照组;雄性SHR32只,随机分为4组,每组8只,即SHR对照组、氨氯地平组(10mg·kg-1·d-1)、阿托伐他汀组(10mg·kg-1·d-1)、联合用药组(氨氯地平10mg·kg-1·d-1及阿托伐他汀10mg·kg-1·d-1)。灌胃给药12wk后,应用形态测量学测定左室质量指数(LVMI),经胸超声心动图测定心室壁厚度、左室重量(LVW)及心脏舒张功能,应用放射免疫法测定大鼠血浆及心肌AngⅡ含量,ELASA法测定血浆BNP含量。结果阿托伐他汀抑制了氨氯地平诱发的循环AngⅡ含量增高[(418±s117)ng·L-1vs(872±128)ng·L-1,P<0.01],降低了心肌AngⅡ含量(P<0.01)。氨氯地平、阿托伐他汀单药及联合用药均明显降低LVMI、血浆BNP含量(均P<0.01),逆转了左室肥厚,这一作用在联合用药时尤为明显(P<0.01)。氨氯地平及阿托伐他汀联合用药明显缩短了SHR的等容舒张时间(IVRT)[(29±4)msvs(40±5)ms,P<0.01]。结论氨氯地平和阿托伐他汀联合用药对高血压左室肥厚及舒张功能的改善具有协同效应,其机制可能与联合用药降低循环及心肌AngⅡ含量有关。

AIM To investigate the synergistic effect of amlodipine and atorvastatin on myocardial and plasma angiotensin Ⅱlevel in spontaneously hypertensive rats （SHRs） , and explore the mechanism of the improvement of left ventricular hypertrophy by drug combination. METHOLDS Eight male Wistar-Kyoto （WKY） rats were chosen as WKY control group with normal pressure; thirty-two male SHRs were randomized into four groups including vehicle-treated SHRs, amlodipine-treated SHRs （10 mg·kg^^-1 ·d^-1） , atorvastatintreated SHRs （10 mg·kg^^-1 ·d^-1）, and combination-treated SHRs （both amlodipine and atorvastatin 10 mg·kg^^-1 ·d^-1）. Drugs were administered by oral garage over 12 weeks. Left ventricular mass index （LVMI） was assessed by morphology method. Left ventricular wall thickness, left ventricular weight （LVW） and diastolic function were detected by transthoracic echocardiography. Plasma and myocardial angiotensin U were determined by radioimmunoassay. Plasma brain natriuretic peptide （BNP） was measured by ELISA. RESULTS The enhanced plasma angiotensin Ⅱ induced by amlodipine were decreased by atorvastatin （（418 ± s 117） ng·L^-1 vs （872 ± 128） ng·L^-1, P 〈 0.01））, myocardial angiotensin Ⅱ level in combination-treated SHR was lower than that in vehicle-treated SHR and amlodipine-treated SHR （both P 〈 0.01 ）. LVMI as well as plasma BNP level was both decreased by amlodipine, atorvastatin monotherapy and combination therapy （all P 〈 0.01） ; furthermore, the combination therapy had the strongest attenuating effects on the development of left ventricular hypertrophy （P 〈 0.01）. The isovolume relaxtion time （IVRT） in combination-treated SHR was obviously shorter than that in vehicle-treated SHR （（29 ± 4） ms vs （40 ± 5） ms, P 〈 0.01 ）. CONCLUSION Amlodipine and atorvastatin have synergistic effects on the improvement of hypertensive cardiac hypertrophy and diastolic dysfunction, which might be related to the decrease of plasma and myocardial angiotensin Ⅱ.