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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。
Objective To observe the effect of amlodipine and atorvastatin monotherapy and combined therapy on spontaneous hypertensive rats (SHR) circulation and myocardial angiotensin Ⅱ (Ang Ⅱ), and to explore the mechanism of combination therapy on left ventricular hypertrophy. Methods Eight male Wistar-Kyoto rats (WKY rats) were randomly divided into 4 groups (n = 8): SHR control group, amlodipine group (10 mg · kg- 1 · d-1), atorvastatin group (10 mg · kg-1 · d-1), combination group (amlodipine 10 mg · kg -1 · d -1 and atorvastatin 10 mg · kg -1 · D-1). After intragastric administration for 12 weeks, the left ventricular mass index (LVMI), the thickness of the ventricular wall, the left ventricular mass (LVW) and the diastolic function were measured by using the morphometric method. The radioimmunoassay Myocardial Ang Ⅱ content, ELASA method for the determination of plasma BNP levels. Results Atorvastatin inhibited the increase of circulating AngⅡ level induced by amlodipine ([418 ± s117] ng · L-1vs (872 ± 128) ng · L-1, P <0.01] <0.01). Both amlodipine and atorvastatin monotherapy and combination therapy significantly reduced LVMI and plasma BNP levels (all P <0.01), reversing left ventricular hypertrophy, especially in combination therapy (P <0.01). Combination of amlodipine and atorvastatin significantly reduced the isovolumetric relaxation time (IVRT) of SHR [(29 ± 4) ms vs (40 ± 5) ms, P <0.01]. Conclusion Combination of amlodipine and atorvastatin has a synergistic effect on the improvement of left ventricular hypertrophy and diastolic function in hypertension. The mechanism may be related to the reduction of circulation and myocardial Ang Ⅱ content by combination therapy.