厄贝沙坦和咪达普利对高血压大鼠心肌细胞外信号调节激酶的影响

Role of the irbesartan and imidapril in the expression of miogen-activated protein kinase and miogen-activated protein kinase phosphatase-1 in myocardium of spontaneously hypertensive rats

目的 探讨血管紧张素Ⅱ受体阻滞剂厄贝沙坦和血管紧张素转换酶抑制剂 (ACEI)咪达普利对高血压大鼠心肌细胞外信号调节激酶 (ERK)和丝裂原活化蛋白激酶磷酸酶 1(MKP 1)的影响。方法 将 2 1只雄性自发性高血压大鼠 (SHR)随机分成 3组 ,每组 7只。其中 2组分别灌喂厄贝沙坦 5 0mg·kg-1·d-1和咪达普利 3mg·kg-1·d-1;对照组给正常饮水 ,并与雄性同周龄WistarKyoto大鼠 (WKY) 6只比较。共 13周 ,用Western blot方法检测大鼠心肌ERK 1和MKP 1。结果 高血压对照组心肌ERK 1明显高于其他三组 (P <0 0 1) ,厄贝沙坦组高于咪达普利组 (P <0 0 5 ) ,与WKY组接近 ;高血压对照组心肌MKP 1也明显高于其他三组 (P <0 0 1) ,厄贝沙坦组高于咪达普利组 (P <0 0 1) ;SHR对照组的心肌ERK 1/MKP 1值仍然明显高于其他三组 ,厄贝沙坦组低于咪达普利组 (P <0 0 5 ) ,两药物干预组的心肌ERK 1/MKP 1与WKY组无显著性差异。结论 血管紧张素Ⅱ受体阻滞剂和ACEI均能通过抑制MAPK途径而抑制左室肥厚 ,厄贝沙坦和咪达普利均能显著抑制心肌的ERK 1和MKP 1,但是抑制ERK 1和MKP 1的强度并不平行 ;厄贝沙坦对MKP的影响较小 ,其对MAPK的总体抑制效应优于咪达普利 ,这种现象可能与刺激血管紧张素Ⅱ受体对MKP

Objective To explore role of the irbesartan and imidapril in the expression of miogen activated protein kinase(MAPK) and miogen activated protein kinase phosphatase 1(MKP 1) in myocardium of spontaneously hypertensive rats(SHR) Methods Twenty one SHR were randomizedly divided into 3 groups, 7 rats each Two groups were fed with irbesartan of 50 mg·kg -1 ·d -1 , imidapril of 3 mg·kg -1 ·d -1 for 13 weeks respectively, while the remained group (SHR control group)and 6 Wistar Kyoto rats(WKY) were routinely given water only for equal time The expression of MAPK and MKP 1 were studied by Western blot Results It was shown that BP dropped markedly ( P <0 01) in both groups fed with irbesartan or with imidapril compared with SHR control group The BP value showed no significant difference between the two therapeutic groups( P >0 05) The heart weight/body weight (HW/BW) decreased markedly( P <0 01) in groups fed with irbesartan or with imidapril, was much lower in irbesartan group than that in imidapril group The expression of ERK 1 (P 44 MARK) in SHR control group was the highest among all the groups ( P <0 01), and higher in irbesartan group than that in imidapril group ( P <0 05) , and similar to that in WKY group It was also shown that MKP 1 expression of SHR control group was the highest among all the groups ( P <0 01), higher in irbesartan group than that in imidapril group ( P <0 01), and similar to that in WKY group It was shown that ERK 1/MKP 1 in SHR control group was still the highest among all the groups, lower in irbesartan group was than that in imidapril group There was no significant difference in ERK 1/MKP 1 between the drug intervened groups and WKY group Conclusion Both irbesartan and imidapril have the effect of suppressing the expression of MKP 1 and ERK 1 in myocardium, but the suppressing effect on MKP 1 and on ERK 1 is not parallel Irbesartan is more effective than imidapril in reducing ERK 1/MKP 1 and may be more effective in proventing left ventricular hypertrophy in patients with hypertension