[Role of valsartan on myocardial Calpain I, calcineurin and Ca/calmodulin-dependent protein kinase IIδ expression of renovascular hypertensive rats].
摘要
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 (CaMKII) δ in the hypertrophic heart, and to investigate the effect of angiotensin II type 1 receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain I, calcineurin and CaMKIIδ in renovascular hypertensive rats model. METHODS: Rats were randomly divided into sham-operated control (n=8), hypertension (n=8) and hypertension plus Val (n=8, 30 mg×kg(-1)×(-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 CaMKIIδ 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 CaMKIIδA and B increased, CaMKIIδC mRNA decreased (P<0.01). Treatment with valsartan effectively attenuated 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 CaMKIIδ signaling pathways.