Role of valsartan on myocardial Calpain Ⅰ , calcineurin and Ca/calmodulin-dependent protein kinase Ⅱ δ expression of renovascular hypertensive rats
10.3760/cma.j.issn.0253-3758.2012.06.012
- VernacularTitle:缬沙坦对肾血管性高血压大鼠心肌钙蛋白酶Ⅰ、钙调神经磷酸酶和钙/钙调素依赖蛋白激酶Ⅱδ的影响
- Author:
Jin-Ya LU
1
;
Jian-Hua ZHU
;
Xiao-Tong QIN
;
Xiao-Hong YU
;
Hong-Zhuan SHENG
Author Information
1. 南通大学附属医院
- Keywords:
Hypertension,renovascular;
Calpain;
Calcineurin;
Ca ( 2 + ) -calmodulindependent protein kinase;
Valsartan
- From:
Chinese Journal of Cardiology
2012;40(6):511-515
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the protein expression of Calpain Ⅰ,mRNA and protein expressions and activity of calcineurin,and the alternative splicing of Ca/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ ) δ in the hypertrophic heart,and to investigate the effect of angiotensin Ⅱ type 1receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain Ⅰ,calcineurin and CaMK Ⅱ δ in renovascular hypertensive rats model.Methods Rats were randomly divided into sharmoperated control (n =8),hypertension (n =8) and hypertension plus Val (n =8,30 mg· kg-1 · d-1 ).The renovascular hypertension was induced by two kidney-one clip methods in rats.The ratio of left ventricular weight to body weight was measured,the mRNA expression of calcineurin and alternative splicing of CaMK Ⅱ δ were determined by RT-PCR,the protein expression of Calpain Ⅰ and calcineurin were measured by Western blot and the activity of calcineurin activity was assayed by a specialized kit.Results Eight weeks after procedure,hypertension rats developed significantly cardiac hypertrophy,and the protein expression of Calpain Ⅰ,mRNA and protein expression and the activity of calcineurin were significantly increased compared sham-operated control rats (all P <0.01 ),the mRNA expression of CaMK Ⅱ δA and B increased,CaMK ⅡδC mRNA decreased ( P <0.01 ).Treatment with valsartan effectively attentated cardiac hypertrophy and reversed hypertension induced changes on myocardial Calpain Ⅰ,calcineurin and CaMKⅡδ.Conclusion Valsartan attenuates cardiac hypertrophy in renovascular hypertensive rats,possibly through inhibiting Calpain Ⅰ,calcineurin and CaMK Ⅱδ signaling pathways.